Bioactive biflavonoids from Wikstroemia indica (L.) C.A. Mey. (Thymelaeaceae): A review
Subject Areas : Natural Products: Isolation and Characterization
1 - OncoWitan, Scientific Consulting Office. Lille (Wasquehal), 59290, France
Keywords: Roots, Phytotherapy, Biflavonoids, Cancer therapeutics, <i>Wikstroemia indica</i> (L.) C.A. Mey,
Abstract :
The roots of the plant Wikstroemia indica (L.) C.A. Mey., also known as Radix Wikstroemiae or Liaogewanggen in China, are used in traditional medicine as decoctions for the treatment of diverse inflammatory diseases, such as arthritis, bronchitis, and many other conditions. A large diversity of bioactive natural products have been characterized in W. indica including flavonoids, lignans, coumarins and sesquiterpenes. A scoping review was designed to identify the variety of biflavonoids isolated to date from the plant (mostly but not exclusively from the roots) and to depict their mode of action, based on database retrieval and a detailed analysis of all the relevant scientific literature. A focus has been made on two important series of C-3 linked dimeric compounds, sikokianins and wikstroflavones, and their anticancer properties and mechanism of action. Sikokianins A-D are atypical C-3/C-3’’ biflavonoids, with sikokianin C as a lead molecule acting as an inhibitor of cystathionine β-synthase (CBS) and exhibiting marked anticancer properties in vivo. Wikstroflavones A-B and wikstaiwanones A-B are unusual flavone/ flavanol dimers with a C-3/C-6'' linkage. Wikstroflavone B can potentiate the antiproliferative and antimetastatic activity of anticancer products. A few other biflavonoids have been isolated from the rhizomes of W. indica, such as daphnodorin derivatives. A biflavonoid-oriented survey of Wikstroemia indica is provided to highlight the potential benefit of the roots of Wikstroemia indica for the treatment of cancer.
Alchetron Encyclopedia, 2018. Wikstroemia indica. https://alchetron.com/Wikstroemia-indica.
Andary, C., Longepierre, D., Le Cong, K., Hul, S., Zaremski, A., Michaloud, G., 2019. Study of a chemotaxonomic marker able to identify the genus Aquilaria (Thymelaeaceae). Bois et Forêts des Tropiques 341, 29-38.
Baba, K., Taniguchiv M., Kozawa, M,, 1994. Three biflavonoids from Wikstroemia sikokiana. Phytochemistry 37, 879-883.
Badawy, A., Hassanean, H., Ibrahim, A.K., Habib, E.S., El-Magd, M.A., Ahmed, S.A, 2021. Isolates from Thymelaea Hirsuta inhibit progression of hepatocellular carcinoma in vitro and in vivo. Nat. Prod. Res. 35, 1799-1807.
Best Chinese Medicines, 2021. Pu Yin - Indian Stringbush - Radix Wikstroemia Indica. https://bestchinesemedicines.com/tags/pu-yin-indian-stringbush-radix-wikstroemia-indica/.
Chang, H., Wang, Y., Gao, X., Song, Z., Awale, S., Han, N., Liu, Z., Yin, J., 2017. Lignans from the root of Wikstroemia indica and their cytotoxic activity against PANC-1 human pancreatic cancer cells. Fitoterapia 121, 31-37.
Chen, C.A., Liu, C.K., Hsu, M.L., Chi, C.W., Ko, C.C., Chen, J.S., Lai, C.T., Chang, H.H., Lee, T.Y., Lai, Y.L., Chen, Y.J., 2017. Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of C-Jun N-terminal kinase. Int. Immunopharmacol. 51, 25-30.
Chen, L.Y., Chen, I.S., Peng, C.F, 2012. Structural elucidation and bioactivity of biflavonoids from the stems of Wikstroemia taiwanensis. Int. J. Mol. Sci. 13, 1029-38.
El-Desoky, A.H.H., Eguchi, K., Kato, H., Kishimoto, N., Misumi, S., Watanabe, T., Tsukamoto, S., 2020. Chamaejasmins, cytotoxic guaiane sesquiterpenes from the root of Stellera chamaejasme L. Fitoterapia 146, 104714.
Feng, G., Chen, Y.L., Li, W., Li, L.L., Wu, Z.G., Wu, Z.J., Hai, Y., Zhang, S.C., Zheng, C.Q., Liu, C.X., He, X., 2018. Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study. Phytomedicine 45, 49-58.
Goossens, J.F., Goossens, L., Bailly, C., 2021. Hinokiflavone and related C-O-C-type biflavonoids as anti-cancer compounds: Properties and mechanism of action. Nat. Prod. Bioprospect. 11, 365-377.
He, X.Y., Liu, Q.C., Peng, W., Huang, Y.L., Wu, C.J., 2013. Bioactivities and serum pharmacochemistry of Qi-Wei-Xiao-Yan-Tang. Pharm. Biol. 51, 629-634.
Huang, W., Li, Y., Wang, H., Su, M., Jiang, Z., Ooi, V.E., Chung, H.Y., 2009. Toxicological study of a Chinese herbal medicine, Wikstroemia indica. Nat. Prod. Commun. 4, 1227-1230.
Huang, W., Zhang, X., Wang, Y., Ye, W., Ooi, V.E., Chung, H.Y., Li, Y., 2010. Antiviral biflavonoids from Radix Wikstroemiae (Liaogewanggen). Chin. Med. 5, 23.
Huang, W.H., Zhou, G.X., Wang, G.C., Chung, H.Y., Ye, W.C., Li, Y.L., 2012. A new biflavonoid with antiviral activity from the roots of Wikstroemia indica. J. Asian Nat. Prod. Res. 14, 401-406.
Kato, M., He, Y.M., Dibwe, D.F., Li, F., Awale, S., Kadota, S., Tezuka, Y, 2014. New guaian-type sesquiterpene from Wikstroemia indica. Nat. Prod. Commun. 9, 1-2.
Ko, Y.C., Feng, H.T., Le.e., R.J., Lee, M.R., 2013. The determination of flavonoids in Wikstroemia indica C. A. Mey. by liquid chromatography with photo-diode array detection and negative electrospray ionization tandem mass spectrometry. Rapid Commun. Mass Spectrom. 27, 59-67.
Lee, S.Y., Park, N.J., Jegal, J., Jo, B.G., Choi, S., Lee, S.W., Uddin, M.S., Kim, S.N., Yang, M.H., 2020. Suppression of DNCB-induced atopic skin lesions in mice by Wikstroemia indica extract. Nutrients 12, 173.
Lei, J.P., Yuan, J.J., Pi, S.H., Wang, R., Tan, R., Ma, C.Y., Zhang, T., Jiang, H.Z., 2017. Flavones and lignans from the stems of Wikstroemia scytophylla Diels. Pharmacogn. Mag. 13, 488-491.
Li, J., Lu, L.Y., Zeng, L.H., Zhang, C., Hu, J.L., Li, X.R., 2012. Sikokianin D, a new C-3/C-3"-biflavanone from the roots of Wikstroemia indica. Molecules 17, 7792-7797.
Li, J., Zhang, J.J., Pang, X.X., ZhengChen, X.L., Gan, L.S., 2014. Biflavanones with anti-proliferative activity against eight human solid tumor cell lines from Stellera chamaejasme. Fitoterapia 93, 163-167.
Li, Y.M., Zhu, L., Jiang, J.G., Yang, L., Wang, D.Y., 2009. Bioactive components and pharmacological action of Wikstroemia indica (L.) C. A. Mey and its clinical application. Curr. Pharm. Biotechnol. 10, 743-752.
Liu, X., Li, Y., Yang, Q., Chen, Y., Weng, X., Wang, Y., Li, N., Zhu, X., 2012. In vitro inhibitory and pro-apoptotic effect of Stellera chamaejasme L extract on human lung cancer cell line NCI-H157. J. Tradit. Chin. Med. 32, 404-410.
Liu, Z., Dong, M., Qiu, X., Han, N., Yin, J., 2021. Diarylpentanones from the root of Wikstroemia indica and their cytotoxic activity against human lung A549 cells. Nat. Prod. Res. 35, 3346-3349.
Liu, Z., Dong, M., Chang, H., Han, N., Yin, J., 2020. Guaiane type of sesquiterpene with NO inhibitory activity from the root of Wikstroemia indica. Bioorg. Chem. 99, 103785.
Lu, C.L., Zhu, L., Piao, J.H., Jiang, J.G., 2012. Chemical compositions extracted from Wikstroemia indica and their multiple activities. Pharm. Biol. 50, 225-231.
Menezes, J.C.J.M.D.S., Campos, V.R., 2021. Natural biflavonoids as potential therapeutic agents against microbial diseases. Sci. Total Environ. 769, 145168.
Mohammadhosseini, M., Venditti, A., Frezza, C., Serafini, M., Bianco, A., Mahdavi, B., 2021a. The genus Haplophyllum Juss.: Phytochemistry and bioactivities-A review. Molecules 26, 4664.
Mohammadhosseini, M, Frezza, C, Venditti, A, Sarker, SD., 2021b. A systematic review on phytochemistry, ethnobotany and biological activities of the genus Bunium L. Chem. Biodivers. 18, e2100317.
Nahar, L., El-Seedi, H.R., Khalifa, S.A.M., Mohammadhosseini, M., Sarker, S.D., 2021. Ruta essential oils: Composition and bioactivities. Molecules 26, 4766.
Niu, W., Chen, F., Wang, J., Qian, J., Yan, S., 2017. Antitumor effect of sikokianin C, a selective cystathionine beta-synthase inhibitor, against human colon cancer in vitro and in vivo. Medchemcomm 9, 113-120.
Niwa, M., Jiang, P.F., Hirata, H., 1986. Two new C-3/C-3’’ biflavanones from Wikstroemia sikokiana. Chem. Pharm. Bull. 34, 3631-3634.
Nunome, S., Ishiyama, A., Kobayashi, M., Otoguro, K., Kiyohara, H., Yamada, H., Omura, S., 2004. In vitro antimalarial activity of biflavonoids from Wikstroemia indica. Planta Med. 70, 76-78.
Phillips, C.M., Zatarain, J.R., Nicholls, M.E., Porter, C., Widen, S.G., Thanki, K., Johnson, P., Jawad, M.U., Moyer, M.P., Randall, J.W., Hellmich, J.L., Maskey, M., Qiu, S., Wood, T.G., Druzhyna, N., Szczesny, B., Módis, K., Szabo, C., Chao, C., Hellmich, M.R., 2017. Upregulation of cystathionine-beta-synthase in colonic epithelia reprograms metabolism and promotes carcinogenesis. Cancer Res. 77, 5741-5754.
Qian, S., Li, M., 2017. Chamaejasmine induces apoptosis in HeLa cells through the PI3K/Akt signaling pathway. Anticancer Drugs 28, 40-50.
Qian, S.J., Zhang, Y.H., Li, G.D., 2020. The complete chloroplast genome of a medicinal plant, Wikstroemia chamaedaphne (Thymelaeaceae). Mitochondrial DNA B Resour. 5, 648-649.
Qian, S.J., Zhang, Y.H., 2019. Characterization of the complete chloroplast genome of a medicinal plant, Wikstroemia indica (Thymelaeaceae). Mitochondrial DNA B Resour. 5, 83-84.
Rahman, K., Chowdhury, A., Islam, F., Barua, S., Rahman, A., 2015. Antidiarrheal and thrombolytic effects of methanol extract of Wikstroemia indica (L.) C. A. Mey leaves. Int. J. Green Pharm. 9, 8-13.
Shao, M., Huang, X.J., Liu, J.S., Han, W.L., Cai, H.B., Tang, Q.F., Fan, Q., 2016. A new cytotoxic biflavonoid from the rhizome of Wikstroemia indica. Nat. Prod. Res. 30, 1417-1422.
Shao, M., Lou, D., Yang, J., Lin, M., Deng, X., Fan, Q., 2020. Curcumin and wikstroflavone B, a new biflavonoid isolated from Wikstroemia indica, synergistically suppress the proliferation and metastasis of nasopharyngeal carcinoma cells via blocking FAK/STAT3 signaling pathway. Phytomedicine 79, 153341.
Si, L., Yan, X., Wang, Y., Ren, B., Ren, H., Ding, Y., Zheng, Q., Li, D., Liu, Y., 2020. Chamaejasmin B decreases malignant characteristics of mouse melanoma B16F0 and B16F10 cells. Front. Oncol. 10, 415.
Sun, L.X., Sun, L.X., Mu, S.X., Wei, L., Xu, C.L., Jia, M.J., 2015. Simultaneous determination of four flavonoids in Wikstroemia indica by HPLC. Zhongguo. Zhong. Yao. Za. Zhi. 40, 700-703.
Suroowan, S., Mahomoodally, F., 2020. Wikstroemia indica. In “Underexplored Medicinal Plants from Sub-Saharan Africa”. Plants with Therapeutic Potential for Human Health. Academic Press. Chapter 45, pp. 295-301.
Suzuki, H., Lee, K.H., Haruna, M., Iida, T., Ito, K., Huang, H.C., 1982. (+)-Arctigenin, a lignan from Wikstroemia indica. Phytochemistry 21, 1824-1824.
Wang, J., Wei, L., Gao, G., Zhu, J., Su, X., Sun, L., 2021. Comprehensive investigation of pharmacodyamic material basis of Wikstroemia indica (L.) C. A. Mey. by serum pharmacochemistry and bivariate correlation analysis. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 1179, 122770.
Wang, J.Y., Gao, G.H., Zhu, J.Q., Wei, L., Sun, L.X., 2019. Chemical profiling from water extract of Wikstroemia indica by UPLC-Q-TOF-MS/MS. Zhongguo Zhong Yao Za Zhi. 44, 3055-3063.
Wang, L.Y., Unehara, T., Kitanaka, S., 2005. Anti-inflammatory activity of new guaiane type sesquiterpene from Wikstroemia indica. Chem. Pharm. Bull. (Tokyo) 53, 137-139.
Wang, Q., Jiang, Y., Luo, C., Wang, R., Liu, S., Huang, X., Shao, M., 2018. Cytotoxic oligophenols from the rhizome of Wikstroemia indica. Bioorg. Med. Chem. Lett. 28, 626-629.
Wang, Y.J., Li, Q., Xiao, H.B., Li, Y.J., Yang, Q., Kan, X.X., Chen, Y., Liu, X.N., Weng, X.G., Chen, X., Cai, W.Y., Guo, Y., Huang, H.F., Zhu, X.X., 2015. Chamaejasmin B exerts anti-MDR effect in vitro and in vivo via initiating mitochondria-dependant intrinsic apoptosis pathway. Drug Des. Devel. Ther. 9, 5301-53013.
Wang, Z.X., Cheng, M.C., Zhang, X.Z., Hong, Z.L., Gao, M.Z., Kan, X.X., Li, Q., Wang, Y.J., Zhu, X.X., Xiao, H.B., 2014. Cytotoxic biflavones from Stellera chamaejasme. Fitoterapia 99, 334-340.
Wei, L., Wang, X., Mu, S., Sun, L., Yu, Z., 2015. Ultra-high-performance liquid chromatography with electrospray ionization tandem mass spectrometry coupled with hierarchical cluster analysis to evaluate Wikstroemia indica (L.) C. A. Mey. from different geographical regions. J. Sep. Sci. 38, 2093-2100.
WFO, 2021. World Flora Online. Published on the Internet; http://www.worldfloraonline.org. Accessed on: 04 Nov 2021.
Xu, Y.J., Capistrano, R., Dhooghe, L., Foubert, K., Lemière, F., Maregesi, S., Baldé, A., Apers, S., Pieters, L., 2011. Herbal medicines and infectious diseases: characterization by LC-SPE-NMR of some medicinal plant extracts used against malaria. Planta Med. 77, 1139-1148.
Yan, R.J., Li, M.Y., Zhou, H.F., Kong, D.Y., Wu, T., 2017. Two new biflavonones from Coreopsis tinctoria. J. Asian Nat. Prod. Res. 19, 960-965.
Yan, Z., Zeng, L., Jin, H., Qin, B., 2015. Potential ecological roles of flavonoids from Stellera chamaejasme. Plant Signal. Behav. 10, e1001225.
Yang, G., Chen, D., 2008. Biflavanones, flavonoids, and coumarins from the roots of Stellera chamaejasme and their antiviral effect on hepatitis B virus. Chem. Biodivers. 5, 1419-1424.
Yang, G., Liao, Z., Xu, Z., Zhang, H., Chen D., 2005. Antimitotic and antifungal C-3/C-3''-biflavanones from Stellera chamaejasme. Chem. Pharm. Bull. (Tokyo) 53, 776-779.
Yao, H., Yuan, Z., Wei, G., Chen, C., Duan, J., Li, Y., Wang, Y., Zhang, C., Liu, Y., 2017. Thevetiaflavone from Wikstroemia indica ameliorates PC12 cells injury induced by OGD/R via improving ROS-mediated mitochondrial dysfunction. Mol. Med. Rep. 16, 9197-9202.
Yao, H., Zhang, W., Wu, H., Yang, M., Wei, P., Ma, H., Duan, J., Zhang, C., Li, Y., 2019. Sikokianin A from Wikstroemia indica protects PC12 cells against OGD/R-induced injury via inhibiting oxidative stress and activating Nrf2. Nat. Prod. Res. 33, 3450-3453.
Yao, H., Zhang, X., Zhang, N., Li, J., Li, Y., Wei, Q., 2021. Wikstromol from Wikstroemia indica induces apoptosis and suppresses migration of MDA-MB-231 cells via inhibiting PI3K/Akt pathway. J. Nat. Med. 75, 178-185.
Yao, H.K., Zhang, W.T., Gao, Y.S., Zhong, Y., 2010. Studies on the chemical constituents of Wikstroemia indica. Zhong. Yao. Cai. 33, 1093-1095.
Zhang, C., Zhou, S.S., Feng, L.Y., Zhang, D.Y., Lin, N.M., Zhang, L.H., Pan, J.P., Wang, J.B., Li, J., 2013. In vitro anti-cancer activity of chamaejasmenin B and neochamaejasmin C isolated from the root of Stellera chamaejasme L. Acta Pharmacol. Sin. 34, 262-270.
Zhang, J.X., He, Z.A., Chen, Z.Y., Wang, Y.X., Bai, S.P., Sun, H.D., 2009. Cytotoxic ent-kaurane diterpenoids from Isodon macrophyllus. J. Asian Nat. Prod. Res. 11, 693-697.
Zhang, X., Wang, G., Huang, W., Ye, W., Li, Y., 2011. Biflavonoids from the roots of Wikstroemia indica. Nat. Prod. Commun. 6, 1111-1114.
Zhao, Y., Wu, F., Wang, Y., Chen, S., Han, G., Liu, M., Jin, D., 2012. Inhibitory action of chamaejasmin A against human HEP-2 epithelial cells: effect on tubulin protein. Mol. Biol. Rep. 39, 11105-11112.
Zheng, W., Gao, X., Gu, Q., Chen, C., Wei, Z., Shi, F., 2007. Antitumor activity of daphnodorins from Daphne genkwa roots. Int. Immunopharmacol. 7, 128-134.
Zhou, D.C., Zheng, G., Jia, L.Y., He, X., Zhang, C.F., Wang, C.Z., Yuan, C.S., 2021. Comprehensive evaluation on anti-inflammatory and anti-angiogenic activities in vitro of fourteen flavonoids from Daphne genkwa based on the combination of efficacy coefficient method and principal component analysis. J. Ethnopharmacol. 268, 113683.
Zhu, H., Blake, S., Chan, K.T., Pearson, R.B., Kang, J., 2018. Cystathionine beta-synthase in physiology and cancer. Biomed. Res. Int. 2018, 3205125.
Zimmerman, C., Austin, P., Khong, A., McLeod, S., Bean, B., Forestieri, R., Andersen, R.J., Jan, E., Roberge, M., Roskelley, C.D., 2013. The small molecule genkwanine M induces single mode, mesenchymal tumor cell motility. Exp. Cell Res. 319, 908-917.
Zuhra, K., Augsburger, F., Majtan, T., Szabo, C., 2020. Cystathionine-beta-Synthase: Molecular regulation and pharmacological inhibition. Biomolecules 10, 697.