An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases

Nand Kishor Roy, Dey Parama, Kishore Banik, Devivasha Bordoloi, Amrita Khwairakpam Devi, Krishan Kumar Thakur, Ganesan Padmavathi, Mehdi Shakibaei, Lu Fan, Gautam Sethi, Ajaikumar B Kunnumakkara, Nand Kishor Roy, Dey Parama, Kishore Banik, Devivasha Bordoloi, Amrita Khwairakpam Devi, Krishan Kumar Thakur, Ganesan Padmavathi, Mehdi Shakibaei, Lu Fan, Gautam Sethi, Ajaikumar B Kunnumakkara

Abstract

Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri. It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson's disease, Alzheimer's, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases.

Keywords: bioavailability; boswellic acid; chronic diseases; molecular targets; pharmacokinetics.

Conflict of interest statement

The authors declare no conflict of interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

Figures

Figure 1
Figure 1
(A) Boswellia (Pankaj Oudhia/www.discoverlife.org) and (B) Boswellia gum resin.
Figure 2
Figure 2
Structure of different triterpenic acids of the Boswellia species.
Figure 3
Figure 3
Molecular targets of Boswellic Acids and their analogues.
Figure 4
Figure 4
Biological activities of Boswellic Acids against diverse chronic diseases.

References

    1. Raghupathi W., Raghupathi V. An Empirical Study of Chronic Diseases in the United States: A Visual Analytics Approach. Int. J. Environ. Res. Public Health. 2018;15:E431. doi: 10.3390/ijerph15030431.
    1. Gautam R., Jachak S.M. Recent developments in anti-inflammatory natural products. Med. Res. Rev. 2009;29:767–820. doi: 10.1002/med.20156.
    1. Neeta, Dureja H. Role of Boswellic Acids in Cancer Treatment. J. Med Sci. 2014;14:261–269.
    1. Behera S., Babu S.M., Ramani Y.R., Choudhury P.K., Panigrahi R. Phytochemical investigation and study on antioxidant properties of Ocimum canum hydro-alcoholic leaf extracts. J. Drug Deliv. Ther. 2012;2:122–128. doi: 10.22270/jddt.v2i4.198.
    1. Banik K., Harsha C., Bordoloi D., Lalduhsaki Sailo B., Sethi G., Leong H.C., Arfuso F., Mishra S., Wang L., Kumar A.P., et al. Therapeutic potential of gambogic acid, a caged xanthone, to target cancer. Cancer Lett. 2018;416:75–86. doi: 10.1016/j.canlet.2017.12.014.
    1. Harsha C., Banik K., Bordoloi D., Kunnumakkara A.B. Antiulcer properties of fruits and vegetables: A mechanism based perspective. Food Chem. Toxicol. 2017;108:104–119. doi: 10.1016/j.fct.2017.07.023.
    1. Deorukhkar A., Krishnan S., Sethi G., Aggarwal B.B. Back to basics: How natural products can provide the basis for new therapeutics. Expert Opin. Investig. Drugs. 2007;16:1753–1773. doi: 10.1517/13543784.16.11.1753.
    1. Yang S.F., Weng C.J., Sethi G., Hu D.N. Natural bioactives and phytochemicals serve in cancer treatment and prevention. Evid. -Based Complementary Altern. Med. 2013;2013:698190. doi: 10.1155/2013/698190.
    1. Tang C.H., Sethi G., Kuo P.L. Novel medicines and strategies in cancer treatment and prevention. Biomed Res. Int. 2014;2014:474078. doi: 10.1155/2014/474078.
    1. Hsieh Y.S., Yang S.F., Sethi G., Hu D.N. Natural bioactives in cancer treatment and prevention. Biomed Res. Int. 2015;2015:182835. doi: 10.1155/2015/182835.
    1. Yarla N.S., Bishayee A., Sethi G., Reddanna P., Kalle A.M., Dhananjaya B.L., Dowluru K.S., Chintala R., Duddukuri G.R. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy. Semin. Cancer Biol. 2016;40–41:48–81. doi: 10.1016/j.semcancer.2016.02.001.
    1. Hasanpourghadi M., Looi C.Y., Pandurangan A.K., Sethi G., Wong W.F., Mustafa M.R. Phytometabolites Targeting the Warburg Effect in Cancer Cells: A Mechanistic Review. Curr. Drug Targets. 2017;18:1086–1094. doi: 10.2174/1389450117666160401124842.
    1. Shanmugam M.K., Warrier S., Kumar A.P., Sethi G., Arfuso F. Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer. Curr. Vasc. Pharmacol. 2017;15:503–519. doi: 10.2174/1570161115666170713094319.
    1. Tewari D., Nabavi S.F., Nabavi S.M., Sureda A., Farooqi A.A., Atanasov A.G., Vacca R.A., Sethi G., Bishayee A. Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention. Pharmacol. Res. 2018;128:366–375. doi: 10.1016/j.phrs.2017.09.014.
    1. Shanmugam M.K., Kannaiyan R., Sethi G. Targeting cell signaling and apoptotic pathways by dietary agents: Role in the prevention and treatment of cancer. Nutr. Cancer. 2011;63:161–173. doi: 10.1080/01635581.2011.523502.
    1. Aggarwal B.B., Sethi G., Baladandayuthapani V., Krishnan S., Shishodia S. Targeting cell signaling pathways for drug discovery: An old lock needs a new key. J. Cell. Biochem. 2007;102:580–592. doi: 10.1002/jcb.21500.
    1. Parikh N.R., Mandal A., Bhatia D., Siveen K.S., Sethi G., Bishayee A. Oleanane triterpenoids in the prevention and therapy of breast cancer: Current evidence and future perspectives. Phytochem. Rev.: Proc. Phytochem. Soc. Eur. 2014;13:793–810. doi: 10.1007/s11101-014-9337-5.
    1. Sethi G., Shanmugam M.K., Warrier S., Merarchi M., Arfuso F., Kumar A.P., Bishayee A. Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review. Nutrients. 2018;10:E645. doi: 10.3390/nu10050645.
    1. Ko J.H., Sethi G., Um J.Y., Shanmugam M.K., Arfuso F., Kumar A.P., Bishayee A., Ahn K.S. The Role of Resveratrol in Cancer Therapy. Int. J. Mol. Sci. 2017;18:E2589. doi: 10.3390/ijms18122589.
    1. Kanchi M.M., Shanmugam M.K., Rane G., Sethi G., Kumar A.P. Tocotrienols: The unsaturated sidekick shifting new paradigms in vitamin E therapeutics. Drug Discov. Today. 2017;22:1765–1781. doi: 10.1016/j.drudis.2017.08.001.
    1. Shanmugam M.K., Arfuso F., Kumar A.P., Wang L., Goh B.C., Ahn K.S., Bishayee A., Sethi G. Modulation of diverse oncogenic transcription factors by thymoquinone, an essential oil compound isolated from the seeds of Nigella sativa Linn. Pharmacol. Res. 2018;129:357–364. doi: 10.1016/j.phrs.2017.11.023.
    1. Ong S.K.L., Shanmugam M.K., Fan L., Fraser S.E., Arfuso F., Ahn K.S., Sethi G., Bishayee A. Focus on Formononetin: Anticancer Potential and Molecular Targets. Cancers. 2019;11:E611. doi: 10.3390/cancers11050611.
    1. Banik K., Ranaware A.M., Deshpande V., Nalawade S.P., Padmavathi G., Bordoloi D., Sailo B.L., Shanmugam M.K., Fan L., Arfuso F., et al. Honokiol for cancer therapeutics: A traditional medicine that can modulate multiple oncogenic targets. Pharmacol. Res. 2019;144:192–209. doi: 10.1016/j.phrs.2019.04.004.
    1. Varughese R.S., Lam W.S., Marican A., Viganeshwari S.H., Bhave A.S., Syn N.L., Wang J., Wong A.L., Kumar A.P., Lobie P.E., et al. Biopharmacological considerations for accelerating drug development of deguelin, a rotenoid with potent chemotherapeutic and chemopreventive potential. Cancer. 2019;125:1789–1798. doi: 10.1002/cncr.32069.
    1. Pathania S., Ramakrishnan S.M., Bagler G. Phytochemica: A platform to explore phytochemicals of medicinal plants. Database. 2015;2015 doi: 10.1093/database/bav075.
    1. Zhang Y.J., Gan R.Y., Li S., Zhou Y., Li A.N., Xu D.P., Li H.B. Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases. Molecules. 2015;20:21138–21156. doi: 10.3390/molecules201219753.
    1. Singh Y.P., Girisa S., Banik K., Ghosh S., Swathi P., Deka M., Padmavathi G., Kotoky J., Sethi G., Fan L., et al. Potential application of zerumbone in the prevention and therapy of chronic human diseases. J. Funct. Foods. 2019;53:248–258. doi: 10.1016/j.jff.2018.12.020.
    1. Merarchi M., Sethi G., Shanmugam M.K., Fan L., Arfuso F., Ahn K.S. Role of Natural Products in Modulating Histone Deacetylases in Cancer. Molecules. 2019;24:E1047. doi: 10.3390/molecules24061047.
    1. Mishra S., Verma S.S., Rai V., Awasthee N., Chava S., Hui K.M., Kumar A.P., Challagundla K.B., Sethi G., Gupta S.C. Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases. Cell. Mol. Life Sci. 2019;76:1947–1966. doi: 10.1007/s00018-019-03053-0.
    1. Yang M.H., Jung S.H., Sethi G., Ahn K.S. Pleiotropic Pharmacological Actions of Capsazepine, a Synthetic Analogue of Capsaicin, against Various Cancers and Inflammatory Diseases. Molecules. 2019;24:E995. doi: 10.3390/molecules24050995.
    1. Deng S., Shanmugam M.K., Kumar A.P., Yap C.T., Sethi G., Bishayee A. Targeting autophagy using natural compounds for cancer prevention and therapy. Cancer. 2019;125:1228–1246. doi: 10.1002/cncr.31978.
    1. Siddiqui M.Z. Boswellia serrata, a potential antiinflammatory agent: An overview. Indian J. Pharm. Sci. 2011;73:255–261.
    1. Al-Yasiry A.R., Kiczorowska B. Frankincense--therapeutic properties. Postepy Hig. I Med. Dosw. 2016;70:380–391. doi: 10.5604/17322693.1200553.
    1. Takahashi M., Sung B., Shen Y., Hur K., Link A., Boland C.R., Aggarwal B.B., Goel A. Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family. Carcinogenesis. 2012;33:2441–2449. doi: 10.1093/carcin/bgs286.
    1. Hamidpour R., Hamidpour S., Hamidpour M., Shahlari M. Frankincense (ru xiang; boswellia species): From the selection of traditional applications to the novel phytotherapy for the prevention and treatment of serious diseases. J. Tradit. Complementary Med. 2013;3:221–226. doi: 10.4103/2225-4110.119723.
    1. Roy N.K., Deka A., Bordoloi D., Mishra S., Kumar A.P., Sethi G., Kunnumakkara A.B. The potential role of boswellic acids in cancer prevention and treatment. Cancer Lett. 2016;377:74–86. doi: 10.1016/j.canlet.2016.04.017.
    1. Buchele B., Zugmaier W., Simmet T. Analysis of pentacyclic triterpenic acids from frankincense gum resins and related phytopharmaceuticals by high-performance liquid chromatography. Identification of lupeolic acid, a novel pentacyclic triterpene. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2003;791:21–30. doi: 10.1016/S1570-0232(03)00160-0.
    1. Safayhi H., Mack T., Sabieraj J., Anazodo M.I., Subramanian L.R., Ammon H.P. Boswellic acids: Novel, specific, nonredox inhibitors of 5-lipoxygenase. J. Pharmacol. Exp. Ther. 1992;261:1143–1146.
    1. Pawar R.K., Shivani S., Singh K.C., Sharma Rajeev K.R. Physicochemical standardisation and development of HPTLC method for the determination of β Boswellic acid from Boswellia serrata Roxb (exudate) Int. J. Appl. Pharm. 2011;3:8–13.
    1. Ammon H.P. Boswellic Acids and Their Role in Chronic Inflammatory Diseases. Adv. Exp. Med. Biol. 2016;928:291–327.
    1. Iram F., Khan S.A., Husain A. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review. Asian Pac. J. Trop. Biomed. 2017;7:513–523. doi: 10.1016/j.apjtb.2017.05.001.
    1. Wang D., Ge S., Bai J., Song Y. Boswellic acid exerts potent anticancer effects in HCT-116 human colon cancer cells mediated via induction of apoptosis, cell cycle arrest, cell migration inhibition and inhibition of PI3K/AKT signalling pathway. J. BUON. 2018;23:340–345.
    1. Akincilar S.C., Low K.C., Liu C.Y., Yan T.D., Oji A., Ikawa M., Li S., Tergaonkar V. Quantitative assessment of telomerase components in cancer cell lines. FEBS Lett. 2015;589:974–984. doi: 10.1016/j.febslet.2015.02.035.
    1. Li Y., Cheng H.S., Chng W.J., Tergaonkar V. Activation of mutant TERT promoter by RAS-ERK signaling is a key step in malignant progression of BRAF-mutant human melanomas. Proc. Natl. Acad. Sci. USA. 2016;113:14402–14407. doi: 10.1073/pnas.1611106113.
    1. Chakraborty S., Lakshmanan M., Swa H.L., Chen J., Zhang X., Ong Y.S., Loo L.S., Akincilar S.C., Gunaratne J., Tergaonkar V., et al. An oncogenic role of Agrin in regulating focal adhesion integrity in hepatocellular carcinoma. Nat. Commun. 2015;6:6184. doi: 10.1038/ncomms7184.
    1. Bordoloi D., Banik K., Shabnam B., Padmavathi G., Monisha J., Arfuso F., Dharmarajan A., Mao X., Lim L.H.K., Wang L., et al. TIPE Family of Proteins and Its Implications in Different Chronic Diseases. Int. J. Mol. Sci. 2018;19:E2974. doi: 10.3390/ijms19102974.
    1. Kunnumakkara A.B., Bordoloi D., Padmavathi G., Monisha J., Roy N.K., Prasad S., Aggarwal B.B. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br. J. Pharmacol. 2017;174:1325–1348. doi: 10.1111/bph.13621.
    1. Sethi G., Sung B., Aggarwal B.B. Nuclear factor-kappaB activation: From bench to bedside. Exp. Biol. Med. 2008;233:21–31. doi: 10.3181/0707-MR-196.
    1. Ahn K.S., Sethi G., Aggarwal B.B. Nuclear factor-kappa B: From clone to clinic. Curr. Mol. Med. 2007;7:619–637. doi: 10.2174/156652407782564363.
    1. Sethi G., Tergaonkar V. Potential pharmacological control of the NF-kappaB pathway. Trends Pharmacol. Sci. 2009;30:313–321. doi: 10.1016/j.tips.2009.03.004.
    1. Li F., Sethi G. Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim. Et Biophys. Acta. 2010;1805:167–180.
    1. Li F., Zhang J., Arfuso F., Chinnathambi A., Zayed M.E., Alharbi S.A., Kumar A.P., Ahn K.S., Sethi G. NF-kappaB in cancer therapy. Arch. Toxicol. 2015;89:711–731. doi: 10.1007/s00204-015-1470-4.
    1. Chai E.Z., Siveen K.S., Shanmugam M.K., Arfuso F., Sethi G. Analysis of the intricate relationship between chronic inflammation and cancer. Biochem. J. 2015;468:1–15. doi: 10.1042/BJ20141337.
    1. Manu K.A., Shanmugam M.K., Ramachandran L., Li F., Fong C.W., Kumar A.P., Tan P., Sethi G. First evidence that gamma-tocotrienol inhibits the growth of human gastric cancer and chemosensitizes it to capecitabine in a xenograft mouse model through the modulation of NF-kappaB pathway. Clin. Cancer Res. 2012;18:2220–2229. doi: 10.1158/1078-0432.CCR-11-2470.
    1. Puar Y.R., Shanmugam M.K., Fan L., Arfuso F., Sethi G., Tergaonkar V. Evidence for the Involvement of the Master Transcription Factor NF-kappaB in Cancer Initiation and Progression. Biomedicines. 2018;6:E82. doi: 10.3390/biomedicines6030082.
    1. Shanmugam M.K., Ahn K.S., Hsu A., Woo C.C., Yuan Y., Tan K.H.B., Chinnathambi A., Alahmadi T.A., Alharbi S.A., Koh A.P.F., et al. Thymoquinone Inhibits Bone Metastasis of Breast Cancer Cells Through Abrogation of the CXCR4 Signaling Axis. Front. Pharmacol. 2018;9:1294. doi: 10.3389/fphar.2018.01294.
    1. Liu L., Ahn K.S., Shanmugam M.K., Wang H., Shen H., Arfuso F., Chinnathambi A., Alharbi S.A., Chang Y., Sethi G., et al. Oleuropein induces apoptosis via abrogating NF-kappaB activation cascade in estrogen receptor-negative breast cancer cells. J. Cell. Biochem. 2019;120:4504–4513. doi: 10.1002/jcb.27738.
    1. Mohan C.D., Bharathkumar H., Dukanya, Rangappa S., Shanmugam M.K., Chinnathambi A., Alharbi S.A., Alahmadi T.A., Bhattacharjee A., Lobie P.E., et al. N-Substituted Pyrido-1,4-Oxazin-3-Ones Induce Apoptosis of Hepatocellular Carcinoma Cells by Targeting NF-kappaB Signaling Pathway. Front. Pharmacol. 2018;9:1125. doi: 10.3389/fphar.2018.01125.
    1. Shanmugam M.K., Ahn K.S., Lee J.H., Kannaiyan R., Mustafa N., Manu K.A., Siveen K.S., Sethi G., Chng W.J., Kumar A.P. Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma. Front. Pharmacol. 2018;9:365. doi: 10.3389/fphar.2018.00365.
    1. Mohan C.D., Anilkumar N.C., Rangappa S., Shanmugam M.K., Mishra S., Chinnathambi A., Alharbi S.A., Bhattacharjee A., Sethi G., Kumar A.P., et al. Novel 1,3,4-Oxadiazole Induces Anticancer Activity by Targeting NF-kappaB in Hepatocellular Carcinoma Cells. Front. Oncol. 2018;8:42. doi: 10.3389/fonc.2018.00042.
    1. Chai E.Z., Shanmugam M.K., Arfuso F., Dharmarajan A., Wang C., Kumar A.P., Samy R.P., Lim L.H., Wang L., Goh B.C., et al. Targeting transcription factor STAT3 for cancer prevention and therapy. Pharmacol. Ther. 2016;162:86–97. doi: 10.1016/j.pharmthera.2015.10.004.
    1. Wong A.L.A., Hirpara J.L., Pervaiz S., Eu J.Q., Sethi G., Goh B.C. Do STAT3 inhibitors have potential in the future for cancer therapy? Expert Opin. Investig. Drugs. 2017;26:883–887. doi: 10.1080/13543784.2017.1351941.
    1. Rajendran P., Ong T.H., Chen L., Li F., Shanmugam M.K., Vali S., Abbasi T., Kapoor S., Sharma A., Kumar A.P., et al. Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo. Clin. Cancer Res. 2011;17:1425–1439. doi: 10.1158/1078-0432.CCR-10-1123.
    1. Siveen K.S., Sikka S., Surana R., Dai X., Zhang J., Kumar A.P., Tan B.K., Sethi G., Bishayee A. Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors. Biochim. Et Biophys. Acta. 2014;1845:136–154. doi: 10.1016/j.bbcan.2013.12.005.
    1. Subramaniam A., Shanmugam M.K., Perumal E., Li F., Nachiyappan A., Dai X., Swamy S.N., Ahn K.S., Kumar A.P., Tan B.K., et al. Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim. Et Biophys. Acta. 2013;1835:46–60. doi: 10.1016/j.bbcan.2012.10.002.
    1. Mohan C.D., Bharathkumar H., Bulusu K.C., Pandey V., Rangappa S., Fuchs J.E., Shanmugam M.K., Dai X., Li F., Deivasigamani A., et al. Development of a novel azaspirane that targets the Janus kinase-signal transducer and activator of transcription (STAT) pathway in hepatocellular carcinoma in vitro and in vivo. J. Biol. Chem. 2014;289:34296–34307. doi: 10.1074/jbc.M114.601104.
    1. Kim C., Lee S.G., Yang W.M., Arfuso F., Um J.Y., Kumar A.P., Bian J., Sethi G., Ahn K.S. Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model. Cancer Lett. 2018;431:123–141. doi: 10.1016/j.canlet.2018.05.038.
    1. Jung Y.Y., Lee J.H., Nam D., Narula A.S., Namjoshi O.A., Blough B.E., Um J.Y., Sethi G., Ahn K.S. Anti-myeloma Effects of Icariin Are Mediated Through the Attenuation of JAK/STAT3-Dependent Signaling Cascade. Front. Pharmacol. 2018;9:531. doi: 10.3389/fphar.2018.00531.
    1. Lee M., Hirpara J.L., Eu J.Q., Sethi G., Wang L., Goh B.C., Wong A.L. Targeting STAT3 and oxidative phosphorylation in oncogene-addicted tumors. Redox Biol. 2018:101073. doi: 10.1016/j.redox.2018.101073.
    1. Arora L., Kumar A.P., Arfuso F., Chng W.J., Sethi G. The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies. Cancers. 2018;10:E327. doi: 10.3390/cancers10090327.
    1. Loh C.Y., Arya A., Naema A.F., Wong W.F., Sethi G., Looi C.Y. Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication. Front. Oncol. 2019;9:48. doi: 10.3389/fonc.2019.00048.
    1. Tan S.M., Li F., Rajendran P., Kumar A.P., Hui K.M., Sethi G. Identification of beta-escin as a novel inhibitor of signal transducer and activator of transcription 3/Janus-activated kinase 2 signaling pathway that suppresses proliferation and induces apoptosis in human hepatocellular carcinoma cells. J. Pharmacol. Exp. Ther. 2010;334:285–293. doi: 10.1124/jpet.110.165498.
    1. Rajendran P., Li F., Manu K.A., Shanmugam M.K., Loo S.Y., Kumar A.P., Sethi G. gamma-Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: Potential role as an antiproliferative, pro-apoptotic and chemosensitizing agent. Br. J. Pharmacol. 2011;163:283–298. doi: 10.1111/j.1476-5381.2010.01187.x.
    1. Rajendran P., Li F., Shanmugam M.K., Vali S., Abbasi T., Kapoor S., Ahn K.S., Kumar A.P., Sethi G. Honokiol inhibits signal transducer and activator of transcription-3 signaling, proliferation, and survival of hepatocellular carcinoma cells via the protein tyrosine phosphatase SHP-1. J. Cell. Physiol. 2012;227:2184–2195. doi: 10.1002/jcp.22954.
    1. Sethi G., Chatterjee S., Rajendran P., Li F., Shanmugam M.K., Wong K.F., Kumar A.P., Senapati P., Behera A.K., Hui K.M., et al. Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo. Mol. Cancer. 2014;13:66. doi: 10.1186/1476-4598-13-66.
    1. Li F., Shanmugam M.K., Chen L., Chatterjee S., Basha J., Kumar A.P., Kundu T.K., Sethi G. Garcinol, a polyisoprenylated benzophenone modulates multiple proinflammatory signaling cascades leading to the suppression of growth and survival of head and neck carcinoma. Cancer Prev. Res. 2013;6:843–854. doi: 10.1158/1940-6207.CAPR-13-0070.
    1. Khattar E., Kumar P., Liu C.Y., Akincilar S.C., Raju A., Lakshmanan M., Maury J.J., Qiang Y., Li S., Tan E.Y., et al. Telomerase reverse transcriptase promotes cancer cell proliferation by augmenting tRNA expression. J. Clin. Investig. 2016;126:4045–4060. doi: 10.1172/JCI86042.
    1. Akincilar S.C., Khattar E., Boon P.L., Unal B., Fullwood M.J., Tergaonkar V. Long-Range Chromatin Interactions Drive Mutant TERT Promoter Activation. Cancer Discov. 2016;6:1276–1291. doi: 10.1158/-16-0177.
    1. Kunnumakkara A.B., Sailo B.L., Banik K., Harsha C., Prasad S., Gupta S.C., Bharti A.C., Aggarwal B.B. Chronic diseases, inflammation, and spices: How are they linked? J. Transl. Med. 2018;16:14. doi: 10.1186/s12967-018-1381-2.
    1. Poeckel D., Werz O. Boswellic acids: Biological actions and molecular targets. Curr. Med. Chem. 2006;13:3359–3369. doi: 10.2174/092986706779010333.
    1. Safayhi H., Rall B., Sailer E.R., Ammon H.P. Inhibition by boswellic acids of human leukocyte elastase. J. Pharmacol. Exp. Ther. 1997;281:460–463.
    1. Sailer E.R., Subramanian L.R., Rall B., Hoernlein R.F., Ammon H.P., Safayhi H. Acetyl-11-keto-beta-boswellic acid (AKBA): Structure requirements for binding and 5-lipoxygenase inhibitory activity. Br. J. Pharmacol. 1996;117:615–618. doi: 10.1111/j.1476-5381.1996.tb15235.x.
    1. Ammon H.P. Boswellic acids (components of frankincense) as the active principle in treatment of chronic inflammatory diseases. Wiener medizinische Wochenschrift. 2002;152:373–378. doi: 10.1046/j.1563-258X.2002.02056.x.
    1. Park Y.S., Lee J.H., Harwalkar J.A., Bondar J., Safayhi H., Golubic M. Acetyl-11-keto-beta-boswellic acid (AKBA) is cytotoxic for meningioma cells and inhibits phosphorylation of the extracellular-signal regulated kinase 1 and 2. Adv. Exp. Med. Biol. 2002;507:387–393.
    1. Syrovets T., Buchele B., Krauss C., Laumonnier Y., Simmet T. Acetyl-boswellic acids inhibit lipopolysaccharide-mediated TNF-alpha induction in monocytes by direct interaction with IkappaB kinases. J. Immunol. 2005;174:498–506. doi: 10.4049/jimmunol.174.1.498.
    1. Cuaz-Perolin C., Billiet L., Bauge E., Copin C., Scott-Algara D., Genze F., Buchele B., Syrovets T., Simmet T., Rouis M. Antiinflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/- mice. Arterioscler. Thromb. Vasc. Biol. 2008;28:272–277. doi: 10.1161/ATVBAHA.107.155606.
    1. Liu J.J., Huang B., Hooi S.C. Acetyl-keto-beta-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells. Br. J. Pharmacol. 2006;148:1099–1107. doi: 10.1038/sj.bjp.0706817.
    1. Syrovets T., Gschwend J.E., Buchele B., Laumonnier Y., Zugmaier W., Genze F., Simmet T. Inhibition of IkappaB kinase activity by acetyl-boswellic acids promotes apoptosis in androgen-independent PC-3 prostate cancer cells in vitro and in vivo. J. Biol. Chem. 2005;280:6170–6180. doi: 10.1074/jbc.M409477200.
    1. Takada Y., Ichikawa H., Badmaev V., Aggarwal B.B. Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression. J. Immunol. 2006;176:3127–3140. doi: 10.4049/jimmunol.176.5.3127.
    1. Park B., Prasad S., Yadav V., Sung B., Aggarwal B.B. Boswellic acid suppresses growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model through modulation of multiple targets. Plos One. 2011;6:e26943. doi: 10.1371/journal.pone.0026943.
    1. Wang R., Wang Y., Gao Z., Qu X. The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC(Min/+) mice. Drug Discov. Ther. 2014;8:25–32. doi: 10.5582/ddt.8.25.
    1. Liu M., Wu Q., Chen P., Buchele B., Bian M., Dong S., Huang D., Ren C., Zhang Y., Hou X., et al. A boswellic acid-containing extract ameliorates schistosomiasis liver granuloma and fibrosis through regulating NF-kappaB signaling in mice. PLoS ONE. 2014;9:e100129.
    1. Qurishi Y., Hamid A., Sharma P.R., Wani Z.A., Mondhe D.M., Singh S.K., Zargar M.A., Andotra S.S., Shah B.A., Taneja S.C., et al. NF-kappaB down-regulation and PARP cleavage by novel 3-alpha-butyryloxy-beta-boswellic acid results in cancer cell specific apoptosis and in vivo tumor regression. Anti-Cancer Agents Med. Chem. 2013;13:777–790. doi: 10.2174/1871520611313050012.
    1. Kumar A., Shah B.A., Singh S., Hamid A., Singh S.K., Sethi V.K., Saxena A.K., Singh J., Taneja S.C. Acyl derivatives of boswellic acids as inhibitors of NF-kappaB and STATs. Bioorganic Med. Chem. Lett. 2012;22:431–435. doi: 10.1016/j.bmcl.2011.10.112.
    1. Hoernlein R.F., Orlikowsky T., Zehrer C., Niethammer D., Sailer E.R., Simmet T., Dannecker G.E., Ammon H.P. Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells and inhibits topoisomerase I. J. Pharmacol. Exp. Ther. 1999;288:613–619.
    1. Zhao W., Entschladen F., Liu H., Niggemann B., Fang Q., Zaenker K.S., Han R. Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. Cancer Detect. Prev. 2003;27:67–75. doi: 10.1016/S0361-090X(02)00170-8.
    1. Chashoo G., Singh S.K., Sharma P.R., Mondhe D.M., Hamid A., Saxena A., Andotra S.S., Shah B.A., Qazi N.A., Taneja S.C., et al. A propionyloxy derivative of 11-keto-beta-boswellic acid induces apoptosis in HL-60 cells mediated through topoisomerase I & II inhibition. Chem.-Biol. Interact. 2011;189:60–71.
    1. Tibaldi E., Zonta F., Bordin L., Magrin E., Gringeri E., Cillo U., Idotta G., Pagano M.A., Brunati A.M. The tyrosine phosphatase SHP-1 inhibits proliferation of activated hepatic stellate cells by impairing PDGF receptor signaling. Biochim. Et Biophys. Acta. 2014;1843:288–298. doi: 10.1016/j.bbamcr.2013.10.010.
    1. Lu M., Xia L., Hua H., Jing Y. Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells. Cancer Res. 2008;68:1180–1186. doi: 10.1158/0008-5472.CAN-07-2978.
    1. Yuan H.Q., Kong F., Wang X.L., Young C.Y., Hu X.Y., Lou H.X. Inhibitory effect of acetyl-11-keto-beta-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells. Biochem. Pharmacol. 2008;75:2112–2121. doi: 10.1016/j.bcp.2008.03.005.
    1. Pang X., Yi Z., Zhang X., Sung B., Qu W., Lian X., Aggarwal B.B., Liu M. Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res. 2009;69:5893–5900. doi: 10.1158/0008-5472.CAN-09-0755.
    1. LoPiccolo J., Granville C.A., Gills J.J., Dennis P.A. Targeting Akt in cancer therapy. Anti-Cancer Drugs. 2007;18:861–874.
    1. Roy N.K., Bordoloi D., Monisha J., Padmavathi G., Kotoky J., Golla R., Kunnumakkara A.B. Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer. Curr. Drug Targets. 2017;18:421–435. doi: 10.2174/1389450117666160307145236.
    1. Kunnumakkara A.B., Banik K., Bordoloi D., Harsha C., Sailo B.L., Padmavathi G., Roy N.K., Gupta S.C., Aggarwal B.B. Googling the Guggul (Commiphora and Boswellia) for Prevention of Chronic Diseases. Front. Pharmacol. 2018;9:686. doi: 10.3389/fphar.2018.00686.
    1. Sharma M.L., Bani S., Singh G.B. Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis. Int. J. Immunopharmacol. 1989;11:647–652. doi: 10.1016/0192-0561(89)90150-1.
    1. Dhaneshwar S., Dipmala P., Abhay H., Prashant B. Disease-modifying effect of anthraquinone prodrug with boswellic acid on collagenase-induced osteoarthritis in Wistar rats. Inflamm. Allergy Drug Targets. 2013;12:288–295.
    1. Wang Q., Pan X., Wong H.H., Wagner C.A., Lahey L.J., Robinson W.H., Sokolove J. Oral and topical boswellic acid attenuates mouse osteoarthritis. Osteoarthr. Cartil. 2014;22:128–132. doi: 10.1016/j.joca.2013.10.012.
    1. Bai F., Chen X., Yang H., Xu H.G. Acetyl-11-Keto-beta-Boswellic Acid Promotes Osteoblast Differentiation by Inhibiting Tumor Necrosis Factor-alpha and Nuclear Factor-kappaB Activity. J. Craniofacial Surg. 2018;29:1996–2002.
    1. Fathi E., Katouli F.H., Riazi G.H., Shasaltaneh M.D., Parandavar E., Bayati S., Afrasiabi A., Nazari R. The Effects of Alpha Boswellic Acid on Reelin Expression and Tau Phosphorylation in Human Astrocytes. Neuromolecular Med. 2017;19:136–146. doi: 10.1007/s12017-016-8437-3.
    1. Liu Z., Liu X., Sang L., Liu H., Xu Q., Liu Z. Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via pSTAT6 inhibition in a murine model of asthma. Int. J. Clin. Exp. Pathol. 2015;8:236–243.
    1. Zhou X., Cai J.G., Zhu W.W., Zhao H.Y., Wang K., Zhang X.F. Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via nhibition of PSTAT6. Genet. Mol. Res. 2015;14:7463–7468. doi: 10.4238/2015.July.3.22.
    1. Mazzio E.A., Lewis C.A., Soliman K.F.A. Transcriptomic Profiling of MDA-MB-231 Cells Exposed to Boswellia Serrata and 3-O-Acetyl-B-Boswellic Acid; ER/UPR Mediated Programmed Cell Death. Cancer Genom. Proteom. 2017;14:409–425.
    1. Frank M.B., Yang Q., Osban J., Azzarello J.T., Saban M.R., Saban R., Ashley R.A., Welter J.C., Fung K.M., Lin H.K. Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity. Bmc Complementary Altern. Med. 2009;9:6. doi: 10.1186/1472-6882-9-6.
    1. Hostanska K., Daum G., Saller R. Cytostatic and apoptosis-inducing activity of boswellic acids toward malignant cell lines in vitro. Anticancer Res. 2002;22:2853–2862.
    1. Qurishi Y., Hamid A., Sharma P.R., Wani Z.A., Mondhe D.M., Singh S.K., Zargar M.A., Andotra S.S., Shah B.A., Taneja S.C., et al. PARP cleavage and perturbance in mitochondrial membrane potential by 3-alpha-propionyloxy-beta-boswellic acid results in cancer cell death and tumor regression in murine models. Future Oncol. 2012;8:867–881. doi: 10.2217/fon.12.68.
    1. Liu J.J., Nilsson A., Oredsson S., Badmaev V., Zhao W.Z., Duan R.D. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis. 2002;23:2087–2093. doi: 10.1093/carcin/23.12.2087.
    1. Shen Y., Takahashi M., Byun H.M., Link A., Sharma N., Balaguer F., Leung H.C., Boland C.R., Goel A. Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells. Cancer Biol. Ther. 2012;13:542–552. doi: 10.4161/cbt.19604.
    1. Girardi B., Principi M., Pricci M., Giorgio F., Iannone A., Losurdo G., Ierardi E., Di Leo A., Barone M. Chemoprevention of inflammation-related colorectal cancer by silymarin-, acetyl-11-keto-beta-boswellic acid-, curcumin- and maltodextrin-enriched dietetic formulation in animal model. Carcinogenesis. 2018;39:1274–1282. doi: 10.1093/carcin/bgy104.
    1. Sayed A.S., El Sayed N.S. Co-administration of 3-Acetyl-11-Keto-Beta-Boswellic Acid Potentiates the Protective Effect of Celecoxib in Lipopolysaccharide-Induced Cognitive Impairment in Mice: Possible Implication of Anti-inflammatory and Antiglutamatergic Pathways. J. Mol. Neurosci. 2016;59:58–67. doi: 10.1007/s12031-016-0734-7.
    1. Agrawal S.S., Saraswati S., Mathur R., Pandey M. Antitumor properties of Boswellic acid against Ehrlich ascites cells bearing mouse. Food Chem. Toxicol. 2011;49:1924–1934. doi: 10.1016/j.fct.2011.04.007.
    1. Moustafa E.M., Thabet N.M., Azab K.S. Boswellic acid disables signal transduction of IL-6-STAT-3 in Ehrlich ascites tumor bearing irradiated mice. Biochem. Cell Biol. 2016;94:307–313. doi: 10.1139/bcb-2015-0169.
    1. Glaser T., Winter S., Groscurth P., Safayhi H., Sailer E.R., Ammon H.P., Schabet M., Weller M. Boswellic acids and malignant glioma: Induction of apoptosis but no modulation of drug sensitivity. Br. J. Cancer. 1999;80:756–765. doi: 10.1038/sj.bjc.6690419.
    1. Ravanan P., Singh S.K., Rao G.S., Kondaiah P. Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates. J. Biosci. 2011;36:297–307. doi: 10.1007/s12038-011-9056-7.
    1. Li W., Liu J., Fu W., Zheng X., Ren L., Liu S., Wang J., Ji T., Du G. 3-O-acetyl-11-keto-beta-boswellic acid exerts anti-tumor effects in glioblastoma by arresting cell cycle at G2/M phase. J. Exp. Clin. Cancer Res. 2018;37:132. doi: 10.1186/s13046-018-0805-4.
    1. Conti S., Vexler A., Edry-Botzer L., Kalich-Philosoph L., Corn B.W., Shtraus N., Meir Y., Hagoel L., Shtabsky A., Marmor S., et al. Combined acetyl-11-keto-beta-boswellic acid and radiation treatment inhibited glioblastoma tumor cells. PLoS ONE. 2018;13:e0198627. doi: 10.1371/journal.pone.0198627.
    1. Jing Y., Nakajo S., Xia L., Nakaya K., Fang Q., Waxman S., Han R. Boswellic acid acetate induces differentiation and apoptosis in leukemia cell lines. Leuk. Res. 1999;23:43–50. doi: 10.1016/S0145-2126(98)00096-4.
    1. Xia L., Chen D., Han R., Fang Q., Waxman S., Jing Y. Boswellic acid acetate induces apoptosis through caspase-mediated pathways in myeloid leukemia cells. Mol. Cancer Ther. 2005;4:381–388.
    1. Khan S., Kaur R., Shah B.A., Malik F., Kumar A., Bhushan S., Jain S.K., Taneja S.C., Singh J. A novel cyano derivative of 11-keto-beta-boswellic acid causes apoptotic death by disrupting PI3K/AKT/Hsp-90 cascade, mitochondrial integrity, and other cell survival signaling events in HL-60 cells. Mol. Carcinog. 2012;51:679–695. doi: 10.1002/mc.20821.
    1. Huang M.T., Badmaev V., Ding Y., Liu Y., Xie J.G., Ho C.T. Anti-tumor and anti-carcinogenic activities of triterpenoid, beta-boswellic acid. Biofactors. 2000;13:225–230. doi: 10.1002/biof.5520130135.
    1. Liu J.J., Nilsson A., Oredsson S., Badmaev V., Duan R.D. Keto- and acetyl-keto-boswellic acids inhibit proliferation and induce apoptosis in Hep G2 cells via a caspase-8 dependent pathway. Int. J. Mol. Med. 2002;10:501–505. doi: 10.3892/ijmm.10.4.501.
    1. Huang G., Yang J., Zhang L., Cao L., Zhang M., Niu X., Zhou Z., Zhang X., Li P., Liu J.F. Inhibitory effect of 11-carbonyl-beta-boswellic acid on non-small cell lung cancer H446 cells. Biochem. Biophys. Res. Commun. 2018;503:2202–2205. doi: 10.1016/j.bbrc.2018.06.137.
    1. Chen M., Wang M., Yang Q., Wang M., Wang Z., Zhu Y., Zhang Y., Wang C., Jia Y., Li Y., et al. Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-beta-boswellic acid in combination on isoproterenol-induced myocardial injury in rats. Int. J. Mol. Med. 2016;37:1501–1510. doi: 10.3892/ijmm.2016.2571.
    1. Pathania A.S., Guru S.K., Kumar S., Kumar A., Ahmad M., Bhushan S., Sharma P.R., Mahajan P., Shah B.A., Sharma S., et al. Interplay between cell cycle and autophagy induced by boswellic acid analog. Sci. Rep. 2016;6:33146. doi: 10.1038/srep33146.
    1. Ameen A.M., Elkazaz A.Y., Mohammad H.M.F., Barakat B.M. Anti-inflammatory and neuroprotective activity of boswellic acids in rotenone parkinsonian rats. Can. J. Physiol. Pharmacol. 2017;95:819–829. doi: 10.1139/cjpp-2016-0158.
    1. Buchele B., Zugmaier W., Estrada A., Genze F., Syrovets T., Paetz C., Schneider B., Simmet T. Characterization of 3alpha-acetyl-11-keto-alpha-boswellic acid, a pentacyclic triterpenoid inducing apoptosis in vitro and in vivo. Planta Med. 2006;72:1285–1289. doi: 10.1055/s-2006-951680.
    1. Morad S.A., Schmid M., Buchele B., Siehl H.U., El Gafaary M., Lunov O., Syrovets T., Simmet T. A novel semisynthetic inhibitor of the FRB domain of mammalian target of rapamycin blocks proliferation and triggers apoptosis in chemoresistant prostate cancer cells. Mol. Pharmacol. 2013;83:531–541. doi: 10.1124/mol.112.081349.
    1. Pathania A.S., Wani Z.A., Guru S.K., Kumar S., Bhushan S., Korkaya H., Seals D.F., Kumar A., Mondhe D.M., Ahmed Z., et al. The anti-angiogenic and cytotoxic effects of the boswellic acid analog BA145 are potentiated by autophagy inhibitors. Mol. Cancer. 2015;14:6. doi: 10.1186/1476-4598-14-6.
    1. Liu Y.Q., Wang S.K., Xu Q.Q., Yuan H.Q., Guo Y.X., Wang Q., Kong F., Lin Z.M., Sun D.Q., Wang R.M., et al. Acetyl-11-keto-beta-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties. Acta Pharmacol. Sin. 2019;40:689–698. doi: 10.1038/s41401-018-0157-9.
    1. Huang M., Li A., Zhao F., Xie X., Li K., Jing Y., Liu D., Zhao L. Design, synthesis and biological evaluation of ring A modified 11-keto-boswellic acid derivatives as Pin1 inhibitors with remarkable anti-prostate cancer activity. Bioorganic Med. Chem. Lett. 2018;28:3187–3193. doi: 10.1016/j.bmcl.2018.08.021.
    1. Wang M.X., Zhao J.X., Meng Y.J., Di T.T., Xu X.L., Xie X.J., Lin Y., Zhang L., Wang N., Li P., et al. Acetyl-11-keto-beta-boswellic acid inhibits the secretion of cytokines by dendritic cells via the TLR7/8 pathway in an imiquimod-induced psoriasis mouse model and in vitro. Life Sci. 2018;207:90–104. doi: 10.1016/j.lfs.2018.05.044.
    1. Bai J., Gao Y., Chen L., Yin Q., Lou F., Wang Z., Xu Z., Zhou H., Li Q., Cai W., et al. Identification of a natural inhibitor of methionine adenosyltransferase 2A regulating one-carbon metabolism in keratinocytes. EBioMedicine. 2019;39:575–590. doi: 10.1016/j.ebiom.2018.12.036.
    1. Xiao B., Zhang G., Ali Sheikh M.S., Shi R. Protective Effects of alpha-Boswellic Acids in a Pulmonary Arterial Hypertensive Rat Model. Planta Med. 2017;83:78–86.
    1. von Rhein C., Weidner T., Henss L., Martin J., Weber C., Sliva K., Schnierle B.S. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro. Antivir. Res. 2016;125:51–57. doi: 10.1016/j.antiviral.2015.11.007.
    1. Kavitha J.V., Rosario J.F., Chandran J., Anbu P., Bakkiyanathan Hypoglycemic and other related effects of Boswellia glabra in alloxan-induced diabetic rats. Indian J. Physiol. Pharmacol. 2007;51:29–39.
    1. Shehata A.M., Quintanilla-Fend L., Bettio S., Singh C.B., Ammon H.P. Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE) Phytomedicine. 2011;18:1037–1044. doi: 10.1016/j.phymed.2011.06.035.
    1. Azemi M.E., Namjoyan F., Khodayar M.J., Ahmadpour F., Darvish Padok A., Panahi M. The Antioxidant Capacity and Anti-diabetic Effect of Boswellia serrata Triana and Planch Aqueous Extract in Fertile Female Diabetic Rats and the Possible Effects on Reproduction and Histological Changes in the Liver and Kidneys. Jundishapur J. Nat. Pharm. Prod. 2012;7:168–175. doi: 10.17795/jjnpp-6755.
    1. Shehata A.M., Quintanilla-Fend L., Bettio S., Jauch J., Scior T., Scherbaum W.A., Ammon H.P. 11-Keto-beta-Boswellic Acids Prevent Development of Autoimmune Reactions, Insulitis and Reduce Hyperglycemia During Induction of Multiple Low-Dose Streptozotocin (MLD-STZ) Diabetes in Mice. Horm. Metab. Res. = Horm. - Und Stoffwechs. = Horm. Et Metab. 2015;47:463–469.
    1. Shehata A.M., Quintanilla-Fend L., Bettio S., Kamyabi-Moghaddam Z., Kohlhofer U.A., Scherbaum W.A., Ammon H.P.T. 11-Keto-beta-Boswellic Acid Inhibits Lymphocyte (CD3) Infiltration Into Pancreatic Islets of Young None Obese Diabetic (NOD) Mice. Horm. Metab. Res. = Horm. - Und Stoffwechs. = Horm. Et Metab. 2017;49:693–700.
    1. Elshazly S.M., Abd El Motteleb D.M., Nassar N.N. The selective 5-LOX inhibitor 11-keto-beta-boswellic acid protects against myocardial ischemia reperfusion injury in rats: Involvement of redox and inflammatory cascades. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2013;386:823–833. doi: 10.1007/s00210-013-0885-9.
    1. Ding Y., Chen M., Wang M., Wang M., Zhang T., Park J., Zhu Y., Guo C., Jia Y., Li Y., et al. Neuroprotection by acetyl-11-keto-beta-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway. Sci. Rep. 2014;4:7002. doi: 10.1038/srep07002.
    1. Ding Y., Chen M., Wang M., Li Y., Wen A. Posttreatment with 11-Keto-beta-Boswellic Acid Ameliorates Cerebral Ischemia-Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism. Mol. Neurobiol. 2015;52:1430–1439. doi: 10.1007/s12035-014-8929-9.
    1. Forouzanfar F., Hosseinzadeh H., Ebrahimzadeh Bideskan A., Sadeghnia H.R. Aqueous and Ethanolic Extracts of Boswellia serrata Protect Against Focal Cerebral Ischemia and Reperfusion Injury in Rats. Phytother. Res. 2016;30:1954–1967. doi: 10.1002/ptr.5701.
    1. Zhang Y., Jia J., Ding Y., Ma Y., Shang P., Liu T., Hui G., Wang L., Wang M., Zhu Z., et al. Alpha-boswellic acid protects against ethanol-induced gastric injury in rats: Involvement of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway. J. Pharm. Pharmacol. 2016;68:514–522. doi: 10.1111/jphp.12532.
    1. Singh S., Khajuria A., Taneja S.C., Khajuria R.K., Singh J., Johri R.K., Qazi G.N. The gastric ulcer protective effect of boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats. Phytomedicine: Int. J. Phytother. Phytopharm. 2008;15:408–415. doi: 10.1016/j.phymed.2008.02.017.
    1. Chen L.C., Hu L.H., Yin M.C. Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury - Corrected and republished from: Biomedicine (Taipei) BioMedicine. 2017;7:13. doi: 10.7603/s40681-016-0009-1.
    1. Barakat B.M., Ahmed H.I., Bahr H.I., Elbahaie A.M. Protective Effect of Boswellic Acids against Doxorubicin-Induced Hepatotoxicity: Impact on Nrf2/HO-1 Defense Pathway. Oxidative Med. Cell. Longev. 2018;2018:8296451. doi: 10.1155/2018/8296451.
    1. Goswami D., Mahapatra A.D., Banerjee S., Kar A., Ojha D., Mukherjee P.K., Chattopadhyay D. Boswellia serrata oleo-gum-resin and beta-boswellic acid inhibits HSV-1 infection in vitro through modulation of NF-small ka, CyrillicB and p38 MAP kinase signaling. Phytomedicine. 2018;51:94–103. doi: 10.1016/j.phymed.2018.10.016.
    1. Xue X., Chen F., Liu A., Sun D., Wu J., Kong F., Luan Y., Qu X., Wang R. Reversal of the multidrug resistance of human ileocecal adenocarcinoma cells by acetyl-11-keto-beta-boswellic acid via downregulation of P-glycoprotein signals. Biosci. Trends. 2016;10:392–399. doi: 10.5582/bst.2016.01115.
    1. Liu M., Liu T., Shang P., Zhang Y., Liu L., Liu T., Sun S. Acetyl-11-keto-beta-boswellic acid ameliorates renal interstitial fibrosis via Klotho/TGF-beta/Smad signalling pathway. J. Cell. Mol. Med. 2018;22:4997–5007. doi: 10.1111/jcmm.13766.
    1. Singh A., Arvinda S., Singh S., Suri J., Koul S., Mondhe D.M., Singh G., Vishwakarma R. IN0523 (Urs-12-ene-3alpha,24beta-diol) a plant based derivative of boswellic acid protect Cisplatin induced urogenital toxicity. Toxicol. Appl. Pharmacol. 2017;318:8–15. doi: 10.1016/j.taap.2017.01.011.
    1. Sayed A.S., Gomaa I.E.O., Bader M., El Sayed N. Role of 3-Acetyl-11-Keto-Beta-Boswellic Acid in Counteracting LPS-Induced Neuroinflammation via Modulation of miRNA-155. Mol. Neurobiol. 2018;55:5798–5808. doi: 10.1007/s12035-017-0801-2.
    1. Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. Global cancer statistics, 2012. Ca: A Cancer J. Clin. 2015;65:87–108. doi: 10.3322/caac.21262.
    1. Girisa S., Shabnam B., Monisha J., Fan L., Halim C.E., Arfuso F., Ahn K.S., Sethi G., Kunnumakkara A.B. Potential of Zerumbone as an Anti-Cancer Agent. Molecules. 2019;24:E734. doi: 10.3390/molecules24040734.
    1. Sailo B.L., Banik K., Girisa S., Bordoloi D., Fan L., Halim C.E., Wang H., Kumar A.P., Zheng D., Mao X., et al. FBXW7 in Cancer: What Has Been Unraveled Thus Far? Cancers. 2019;11 doi: 10.3390/cancers11020246.
    1. Shabnam B., Padmavathi G., Banik K., Girisa S., Monisha J., Sethi G., Fan L., Wang L., Mao X., Kunnumakkara A.B. Sorcin a Potential Molecular Target for Cancer Therapy. Transl. Oncol. 2018;11:1379–1389. doi: 10.1016/j.tranon.2018.08.015.
    1. Monisha J., Jaiswal A., Banik K., Choudhary H., Singh A.K., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Cancer Cell Chemoresistance: A Prime Obstacle in Cancer Therapy; pp. 15–49.
    1. Ranaware A.M., Banik K., Deshpande V., Padmavathi G., Roy N.K., Sethi G., Fan L., Kumar A.P., Kunnumakkara A.B. Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer. Int. J. Mol. Sci. 2018;19:E2362. doi: 10.3390/ijms19082362.
    1. Kunnumakkara A.B., Bordoloi D., Sailo B.L., Roy N.K., Thakur K.K., Banik K., Shakibaei M., Gupta S.C., Aggarwal B.B. Cancer drug development: The missing links. Exp. Biol. Med. 2019;244:663–689. doi: 10.1177/1535370219839163.
    1. Sailo B.L., Banik K., Padmavathi G., Javadi M., Bordoloi D., Kunnumakkara A.B. Tocotrienols: The promising analogues of vitamin E for cancer therapeutics. Pharmacol. Res. 2018;130:259–272. doi: 10.1016/j.phrs.2018.02.017.
    1. Padmavathi G., Rathnakaram S.R., Monisha J., Bordoloi D., Roy N.K., Kunnumakkara A.B. Potential of butein, a tetrahydroxychalcone to obliterate cancer. Phytomedicine. 2015;22:1163–1171. doi: 10.1016/j.phymed.2015.08.015.
    1. Bordoloi D., Roy N.K., Monisha J., Padmavathi G., Kunnumakkara A.B. Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far. Recent Pat. Anti-Cancer Drug Discov. 2016;11:67–97. doi: 10.2174/1574892810666151020101706.
    1. Varoni E.M., Lo Faro A.F., Sharifi-Rad J., Iriti M. Anticancer Molecular Mechanisms of Resveratrol. Front. Nutr. 2016;3:8. doi: 10.3389/fnut.2016.00008.
    1. Shanmugam M.K., Lee J.H., Chai E.Z., Kanchi M.M., Kar S., Arfuso F., Dharmarajan A., Kumar A.P., Ramar P.S., Looi C.Y., et al. Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin. Cancer Biol. 2016;40–41:35–47. doi: 10.1016/j.semcancer.2016.03.005.
    1. Roy N.K., Sharma A., Singh A.K., Bordoloi D., Sailo B.L., Monisha J., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Bladder Cancer: Chemoresistance and Chemosensitization; pp. 51–80.
    1. Khwairakpam A.D., Monisha J., Banik K., Choudhary H., Sharma A., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Chemoresistance in Brain Cancer and Different Chemosensitization Approaches; pp. 107–127.
    1. Banik K., Sailo B.L., Thakur K.K., Jaiswal A., Monisha J., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Potential of Different Chemosensitizers to Overcome Chemoresistance in Cervical Cancer; pp. 163–179.
    1. Toden S., Okugawa Y., Buhrmann C., Nattamai D., Anguiano E., Baldwin N., Shakibaei M., Boland C.R., Goel A. Novel Evidence for Curcumin and Boswellic Acid-Induced Chemoprevention through Regulation of miR-34a and miR-27a in Colorectal Cancer. Cancer Prev. Res. 2015;8:431–443. doi: 10.1158/1940-6207.CAPR-14-0354.
    1. Singh A.K., Roy N.K., Anip A., Banik K., Monisha J., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Different Methods to Inhibit Chemoresistance in Hepatocellular Carcinoma; pp. 373–398.
    1. Siveen K.S., Ahn K.S., Ong T.H., Shanmugam M.K., Li F., Yap W.N., Kumar A.P., Fong C.W., Tergaonkar V., Hui K.M., et al. Y-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model. Oncotarget. 2014;5:1897–1911. doi: 10.18632/oncotarget.1876.
    1. Swamy S.G., Kameshwar V.H., Shubha P.B., Looi C.Y., Shanmugam M.K., Arfuso F., Dharmarajan A., Sethi G., Shivananju N.S., Bishayee A. Targeting multiple oncogenic pathways for the treatment of hepatocellular carcinoma. Target. Oncol. 2017;12:1–10. doi: 10.1007/s11523-016-0452-7.
    1. Dai X., Ahn K.S., Wang L.Z., Kim C., Deivasigamni A., Arfuso F., Um J.Y., Kumar A.P., Chang Y.C., Kumar D., et al. Ascochlorin Enhances the Sensitivity of Doxorubicin Leading to the Reversal of Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma. Mol. Cancer Ther. 2016;15:2966–2976. doi: 10.1158/1535-7163.MCT-16-0391.
    1. Dai X., Wang L., Deivasigamni A., Looi C.Y., Karthikeyan C., Trivedi P., Chinnathambi A., Alharbi S.A., Arfuso F., Dharmarajan A., et al. A novel benzimidazole derivative, MBIC inhibits tumor growth and promotes apoptosis via activation of ROS-dependent JNK signaling pathway in hepatocellular carcinoma. Oncotarget. 2017;8:12831–12842. doi: 10.18632/oncotarget.14606.
    1. Dai X., Ahn K.S., Kim C., Siveen K.S., Ong T.H., Shanmugam M.K., Li F., Shi J., Kumar A.P., Wang L.Z., et al. Ascochlorin, an isoprenoid antibiotic inhibits growth and invasion of hepatocellular carcinoma by targeting STAT3 signaling cascade through the induction of PIAS3. Mol. Oncol. 2015;9:818–833. doi: 10.1016/j.molonc.2014.12.008.
    1. Subramaniam A., Shanmugam M.K., Ong T.H., Li F., Perumal E., Chen L., Vali S., Abbasi T., Kapoor S., Ahn K.S., et al. Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3. Br. J. Pharmacol. 2013;170:807–821. doi: 10.1111/bph.12302.
    1. Manu K.A., Shanmugam M.K., Ong T.H., Subramaniam A., Siveen K.S., Perumal E., Samy R.P., Bist P., Lim L.H., Kumar A.P., et al. Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS ONE. 2013;8:e57015. doi: 10.1371/journal.pone.0057015.
    1. Khan M.A., Singh M., Khan M.S., Najmi A.K., Ahmad S. Caspase mediated synergistic effect of Boswellia serrata extract in combination with doxorubicin against human hepatocellular carcinoma. Biomed Res. Int. 2014;2014:294143. doi: 10.1155/2014/294143.
    1. Padmavathi G., Monisha J., Banik K., Thakur K.K., Choudhary H., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Different Chemosensitization Approaches to Overcome Chemoresistance in Prostate Cancer; pp. 583–613.
    1. Sikka S., Chen L., Sethi G., Kumar A.P. Targeting PPARgamma Signaling Cascade for the Prevention and Treatment of Prostate Cancer. Ppar Res. 2012;2012:968040. doi: 10.1155/2012/968040.
    1. Zhang J., Ahn K.S., Kim C., Shanmugam M.K., Siveen K.S., Arfuso F., Samym R.P., Deivasigamanim A., Lim L.H., Wang L., et al. Nimbolide-Induced Oxidative Stress Abrogates STAT3 Signaling Cascade and Inhibits Tumor Growth in Transgenic Adenocarcinoma of Mouse Prostate Model. Antioxid. Redox Signal. 2016;24:575–589. doi: 10.1089/ars.2015.6418.
    1. Zhang J., Sikka S., Siveen K.S., Lee J.H., Um J.Y., Kumar A.P., Chinnathambi A., Alharbi S.A., Basappa, Rangappa K.S., et al. Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer. Apoptosis. 2017;22:158–168. doi: 10.1007/s10495-016-1313-7.
    1. Lee J.H., Kim C., Baek S.H., Ko J.H., Lee S.G., Yang W.M., Um J.Y., Sethi G., Ahn K.S. Capsazepine inhibits JAK/STAT3 signaling, tumor growth, and cell survival in prostate cancer. Oncotarget. 2017;8:17700–17711. doi: 10.18632/oncotarget.10775.
    1. Kim S.W., Kim S.M., Bae H., Nam D., Lee J.H., Lee S.G., Shim B.S., Kim S.H., Ahn K.S., Choi S.H., et al. Embelin inhibits growth and induces apoptosis through the suppression of Akt/mTOR/S6K1 signaling cascades. Prostate. 2013;73:296–305. doi: 10.1002/pros.22574.
    1. Sailo B.L., Monisha J., Jaiswal A., Prakash J., Roy N.K., Thakur K.K., Banik K., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Molecular Alterations Involved in Pancreatic Cancer Chemoresistance and Chemosensitization Strategies; pp. 557–581.
    1. Yadav V.R., Prasad S., Sung B., Gelovani J.G., Guha S., Krishnan S., Aggarwal B.B. Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers. Int. J. Cancer. 2012;130:2176–2184. doi: 10.1002/ijc.26251.
    1. Monisha J., Roy N.K., Sharma A., Banik K., Padmavathi G., Bordoloi D., Kunnumakkara A.B. Cancer Cell Chemoresistance and Chemosensitization. World Scientific; Singapore: 2018. Chemoresistance and Chemosensitization in Melanoma; pp. 479–527.
    1. Kolios G. Animal models of inflammatory bowel disease: How useful are they really? Curr. Opin. Gastroenterol. 2016;32:251–257. doi: 10.1097/MOG.0000000000000287.
    1. Gupta I., Parihar A., Malhotra P., Singh G.B., Ludtke R., Safayhi H., Ammon H.P. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur. J. Med Res. 1997;2:37–43.
    1. Krieglstein C.F., Anthoni C., Rijcken E.J., Laukotter M., Spiegel H.U., Boden S.E., Schweizer S., Safayhi H., Senninger N., Schurmann G. Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis. Int. J. Colorectal Dis. 2001;16:88–95. doi: 10.1007/s003840100292.
    1. Kiela P.R., Midura A.J., Kuscuoglu N., Jolad S.D., Solyom A.M., Besselsen D.G., Timmermann B.N., Ghishan F.K. Effects of Boswellia serrata in mouse models of chemically induced colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2005;288:G798–G808. doi: 10.1152/ajpgi.00433.2004.
    1. Anthoni C., Laukoetter M.G., Rijcken E., Vowinkel T., Mennigen R., Muller S., Senninger N., Russell J., Jauch J., Bergmann J., et al. Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2006;290:G1131–G1137. doi: 10.1152/ajpgi.00562.2005.
    1. Al-Haddad R., Karnib N., Assaad R.A., Bilen Y., Emmanuel N., Ghanem A., Younes J., Zibara V., Stephan J.S., Sleiman S.F. Epigenetic changes in diabetes. Neurosci. Lett. 2016;625:64–69. doi: 10.1016/j.neulet.2016.04.046.
    1. Ahangarpour A., Heidari H., Fatemeh R.A., Pakmehr M., Shahbazian H., Ahmadi I., Mombeini Z., Mehrangiz B.H. Effect of Boswellia serrata supplementation on blood lipid, hepatic enzymes and fructosamine levels in type2 diabetic patients. J. Diabetes Metab. Disord. 2014;13:29. doi: 10.1186/2251-6581-13-29.
    1. Ebrahimpour S., Fazeli M., Mehri S., Taherianfard M., Hosseinzadeh H. Boswellic Acid Improves Cognitive Function in a Rat Model Through Its Antioxidant Activity: - Neuroprotective effect of Boswellic acid. J. Pharmacopunct. 2017;20:10–17.
    1. Prieto-Moure B., Lloris-Carsi J.M., Barrios-Pitarque C., Toledo-Pereyra L.H., Lajara-Romance J.M., Berda-Antoli M., Lloris-Cejalvo J.M., Cejalvo-Lapena D. Pharmacology of Ischemia-Reperfusion. Translational Research Considerations. J. Investig. Surg. 2016;29:234–249. doi: 10.3109/08941939.2015.1119219.
    1. Wildfeuer A., Neu I.S., Safayhi H., Metzger G., Wehrmann M., Vogel U., Ammon H.P. Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis. Arzneim.-Forsch. 1998;48:668–674.
    1. Chen L.C., Hu L.H., Yin M.C. Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury. Biomedicine. 2016;6:9. doi: 10.7603/s40681-016-0009-1.
    1. Majeed M., Majeed S., Narayanan N.K., Nagabhushanam K. A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee. Phytother. Res. PTR. 2019;33:1457–1468. doi: 10.1002/ptr.6338.
    1. Sengupta K., Alluri K.V., Satish A.R., Mishra S., Golakoti T., Sarma K.V., Dey D., Raychaudhuri S.P. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res. Ther. 2008;10:R85. doi: 10.1186/ar2461.
    1. Haroyan A., Mukuchyan V., Mkrtchyan N., Minasyan N., Gasparyan S., Sargsyan A., Narimanyan M., Hovhannisyan A. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: A comparative, randomized, double-blind, placebo-controlled study. BMC Complementary Altern. Med. 2018;18:7. doi: 10.1186/s12906-017-2062-z.
    1. Notarnicola A., Maccagnano G., Moretti L., Pesce V., Tafuri S., Fiore A., Moretti B. Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial. Int. J. Immunopathol. Pharmacol. 2016;29:140–146. doi: 10.1177/0394632015622215.
    1. Notarnicola A., Tafuri S., Fusaro L., Moretti L., Pesce V., Moretti B. The "MESACA" study: Methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis. Adv. Ther. 2011;28:894–906. doi: 10.1007/s12325-011-0068-3.
    1. Riva A., Giacomelli L., Togni S., Franceschi F., Eggenhoffner R., Zuccarini M.C., Belcaro G. Oral administration of a lecithin-based delivery form of boswellic acids (Casperome(R)) for the prevention of symptoms of irritable bowel syndrome: A randomized clinical study. Minerva Gastroenterol. E Dietol. 2019;65:30–35. doi: 10.23736/S1121-421X.18.02530-8.
    1. Gupta I., Gupta V., Parihar A., Gupta S., Ludtke R., Safayhi H., Ammon H.P. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur. J. Med. Res. 1998;3:511–514.
    1. Kirste S., Treier M., Wehrle S.J., Becker G., Abdel-Tawab M., Gerbeth K., Hug M.J., Lubrich B., Grosu A.L., Momm F. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: A prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011;117:3788–3795. doi: 10.1002/cncr.25945.
    1. Gerhardt H., Seifert F., Buvari P., Vogelsang H., Repges R. Therapy of active Crohn disease with Boswellia serrata extract H 15. Z. Fur Gastroenterol. 2001;39:11–17. doi: 10.1055/s-2001-10708.
    1. Togni S., Maramaldi G., Di Pierro F., Biondi M. A cosmeceutical formulation based on boswellic acids for the treatment of erythematous eczema and psoriasis. Clin. Cosmet. Investig. Derm. 2014;7:321–327.
    1. Calzavara-Pinton P., Zane C., Facchinetti E., Capezzera R., Pedretti A. Topical Boswellic acids for treatment of photoaged skin. Dermatol. Ther. 2010;23(Suppl 1):S28–S32. doi: 10.1111/j.1529-8019.2009.01284.x.
    1. Pedretti A., Capezzera R., Zane C., Facchinetti E., Calzavara-Pinton P. Effects of topical boswellic acid on photo and age-damaged skin: Clinical, biophysical, and echographic evaluations in a double-blind, randomized, split-face study. Planta Med. 2010;76:555–560. doi: 10.1055/s-0029-1240581.
    1. Sterk V., Buchele B., Simmet T. Effect of food intake on the bioavailability of boswellic acids from a herbal preparation in healthy volunteers. Planta Med. 2004;70:1155–1160. doi: 10.1055/s-2004-835844.
    1. Tawab M.A., Kaunzinger A., Bahr U., Karas M., Wurglics M., Schubert-Zsilavecz M. Development of a high-performance liquid chromatographic method for the determination of 11-keto-beta-boswellic acid in human plasma. J. Chromatogr. BBiomed. Sci. Appl. 2001;761:221–227. doi: 10.1016/S0378-4347(01)00335-8.
    1. Buchele B., Simmet T. Analysis of 12 different pentacyclic triterpenic acids from frankincense in human plasma by high-performance liquid chromatography and photodiode array detection. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2003;795:355–362. doi: 10.1016/S1570-0232(03)00555-5.
    1. Sharma S., Thawani V., Hingorani L., Shrivastava M., Bhate V.R., Khiyani R. Pharmacokinetic study of 11-Keto beta-Boswellic acid. Phytomedicine. 2004;11:255–260. doi: 10.1078/0944-7113-00290.
    1. Reising K., Meins J., Bastian B., Eckert G., Mueller W.E., Schubert-Zsilavecz M., Abdel-Tawab M. Determination of boswellic acids in brain and plasma by high-performance liquid chromatography/tandem mass spectrometry. Anal. Chem. 2005;77:6640–6645. doi: 10.1021/ac0506478.
    1. Kruger P., Daneshfar R., Eckert G.P., Klein J., Volmer D.A., Bahr U., Muller W.E., Karas M., Schubert-Zsilavecz M., Abdel-Tawab M. Metabolism of boswellic acids in vitro and in vivo. Drug Metab. Dispos. 2008;36:1135–1142. doi: 10.1124/dmd.107.018424.
    1. Bagul P., Khomane K.S., Bansal A.K. Investigating permeability related hurdles in oral delivery of 11-keto-beta-boswellic acid. Int. J. Pharm. 2014;464:104–110. doi: 10.1016/j.ijpharm.2014.01.019.
    1. Gerbeth K., Husch J., Fricker G., Werz O., Schubert-Zsilavecz M., Abdel-Tawab M. In vitro metabolism, permeation, and brain availability of six major boswellic acids from Boswellia serrata gum resins. Fitoterapia. 2013;84:99–106. doi: 10.1016/j.fitote.2012.10.009.
    1. Wang Y., Sun Y., Wang C., Huo X., Liu P., Wang C., Zhang B., Zhan L., Zhang H., Deng S., et al. Biotransformation of 11-keto-beta-boswellic acid by Cunninghamella blakesleana. Phytochemistry. 2013;96:330–336. doi: 10.1016/j.phytochem.2013.07.018.
    1. Du Z., Liu Z., Ning Z., Liu Y., Song Z., Wang C., Lu A. Prospects of boswellic acids as potential pharmaceutics. Planta Med. 2015;81:259–271. doi: 10.1055/s-0034-1396313.
    1. Skarke C., Kuczka K., Tausch L., Werz O., Rossmanith T., Barrett J.S., Harder S., Holtmeier W., Schwarz J.A. Increased bioavailability of 11-keto-beta-boswellic acid following single oral dose frankincense extract administration after a standardized meal in healthy male volunteers: Modeling and simulation considerations for evaluating drug exposures. J. Clin. Pharmacol. 2012;52:1592–1600. doi: 10.1177/0091270011422811.
    1. Kruger P., Kanzer J., Hummel J., Fricker G., Schubert-Zsilavecz M., Abdel-Tawab M. Permeation of Boswellia extract in the Caco-2 model and possible interactions of its constituents KBA and AKBA with OATP1B3 and MRP2. Eur. J. Pharm. Sci. 2009;36:275–284. doi: 10.1016/j.ejps.2008.10.005.
    1. Husch J., Bohnet J., Fricker G., Skarke C., Artaria C., Appendino G., Schubert-Zsilavecz M., Abdel-Tawab M. Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome((R))) of Boswellia extract. Fitoterapia. 2013;84:89–98. doi: 10.1016/j.fitote.2012.10.002.
    1. Aqil F., Munagala R., Jeyabalan J., Vadhanam M.V. Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Lett. 2013;334:133–141. doi: 10.1016/j.canlet.2013.02.032.
    1. Wang S., Su R., Nie S., Sun M., Zhang J., Wu D., Moustaid-Moussa N. Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. J. Nutr. Biochem. 2014;25:363–376. doi: 10.1016/j.jnutbio.2013.10.002.
    1. Riva A., Morazzoni P., Artaria C., Allegrini P., Meins J., Savio D., Appendino G., Schubert-Zsilavecz M., Abdel-Tawab M. A single-dose, randomized, cross-over, two-way, open-label study for comparing the absorption of boswellic acids and its lecithin formulation. Phytomedicine. 2016;23:1375–1382. doi: 10.1016/j.phymed.2016.07.009.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa