191
Views
0
CrossRef citations to date
0
Altmetric
Review Article

A critical assessment of the whole plant-based phytotherapeutics from Withania somnifera (L.) Dunal with respect to safety and efficacy vis-a-vis leaf or root extract-based formulation

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 698-706 | Received 12 Jun 2023, Accepted 26 Jul 2023, Published online: 14 Aug 2023

References

  • Abouzid SF, El-Bassuony AA, Nasib A, Khan S, Qureshi J, Choudhary MI. 2010. Withaferin A production by root cultures of Withania coagulans. Int J Appl Res Nat Prod. 3(1): 23–27.
  • Agarwal AV, Singh D, Dhar YV, Michael R, Gupta P, Chandra D, Trivedi PK. 2018. Virus-induced silencing of key genes leads to differential impact on withanolide biosynthesis in the medicinal plant, Withania somnifera. Plant Cell Physiol. 59(2):262–274. doi: 10.1093/pcp/pcx179.
  • Ajgaonkar A, Jain M, Debnath K. 2022. Efficacy and safety of Ashwagandha (Withania somnifera) root extract for improvement of sexual health in healthy women: A prospective, randomized, placebo-controlled study. Cureus 14(10): e30787. doi: 10.7759/cureus.30787.
  • Antony ML, Lee J, Hahm ER, Kim SH, Marcus AI, Kumari V, Ji X, Yang Z, Vowell CL, Wipf P, Uechi GT, Yates NA, Romero G, Sarkar SN, Singh SV. 2014. Growth arrest by the antitumor steroidal lactone withaferin A in human breast cancer cells is associated with down-regulation and covalent binding at cysteine 303 of β-tubulin. J Biol Chem. 289(3):1852–1865. doi: 10.1074/jbc.M113.496844.
  • Atteeq M. 2022. Evaluating anticancer properties of withaferin A—a potent phytochemical. Front Pharmacol. 13: 975320. doi: 10.3389/fphar.2022.975320.
  • Balkrishna A, Sinha S, Srivastava J, Varshney A. 2022. Withania somnifera (L.) Dunal whole-plant extract demonstrates acceptable non-clinical safety in rat 28-day subacute toxicity evaluation under GLP-compliance. Sci Rep. 12(1):11047. doi: 10.1038/s41598-022-14944-x.
  • Björnsson HK, Björnsson ES, Avula B, Khan IA, Jonasson JG, Ghabril M, Hayashi PH, Navarro V. 2020. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 40(4): 825–829. doi: 10.1111/liv.14393.
  • Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martínez A, Kreider RB. 2021. Effects of Ashwagandha (Withania somnifera) on physical performance: Systematic review and Bayesian meta-analysis. J Funct Morphol Kinesiol. 6(1): 20. doi: 10.3390/jfmk6010020.
  • Carioscia JA, Stansbury JW, Bowman CN. 2007. Evaluation and control of thiol-ene/thiol-epoxy hybrid networks. Polymer (Guildf). 48(6):1526–1532. doi: 10.1016/j.polymer.2007.
  • Chandrasekhar K, Kapoor J, Anishetty S. 2012. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med. 34(3): 255–262. doi: 10.4103/0253-7176.106022.
  • Chauhan S, Srivastava MK, Pathak AK. 2022. Effect of standardized root extract of ashwagandha (Withania somnifera) on well-being and sexual performance in adult males: a randomized controlled trial. Health Sci Rep. 5:e741. doi: 10.1002/hsr2.741.
  • Chaurasiya ND, Uniyal GC, Lal P, Misra L, Sangwan NS, Tuli R, Sangwan RS. 2008. Analysis of withanolides in root and leaf of Withania somnifera by HPLC with photodiode array and evaporative light scattering detection. Phytochem Anal. 19(2):148–154. doi: 10.1002/pca.1029.
  • Chaurasiya ND, Sangwan NS, Sabir F, Misra L, Sangwan RS. 2012. Withanolide biosynthesis recruits both mevalonate and DOXP pathways of isoprenogenesis in Ashwagandha Withania somnifera L. (Dunal). Plant Cell Rep. 31(10):1889–1897. doi: 10.1007/s00299-012-1302-4.
  • Choi BY, Kim BW. 2015. Withaferin-A inhibits colon cancer cell growth by blocking STAT3 transcriptional activity. J Cancer Prevent. 20(3):185–192. doi: 10.15430/JCP.2015.20.3.185.
  • Dadfar SMM, Sekula-Neuner S, Trouillet V, Hirtz M. 2021. Protein microarray immobilization via epoxide ring-opening by thiol, amine, and azide. Adv Mater Interfaces 8, 2002117. doi: 10.1002/admi.202002117.
  • Dhar N, Razdan S, Rana S, Bhat WW, Vishwakarma R, Lattoo SK. 2015. A decade of molecular understanding of withanolide biosynthesis and in vitro studies in Withania somnifera (L.) Dunal: Prospects and perspectives for pathway engineering. Front Plant Sci. 6:1031. doi: 10.3389/fpls.2015.01031.
  • Erb M, Kliebenstein DJ. 2020. Plant secondary metabolites as defenses, regulators, and primary metabolites: The blurred functional trichotomy. Plant Physiol. 184(1):39–52. doi: 10.1104/pp.20.00433.
  • Fazil MHUT, Chirumamilla CS, Perez-Novo C, Wong BHS, Kumar S, Sze SK, Vanden Berghe W, Verma NK. 2021. The steroidal lactone withaferin A impedes T-cell motility by inhibiting the kinase ZAP70 and subsequent kinome signaling. J Biol Chem. 297(6): 101377. doi: 10.1016/j.jbc.2021.101377.
  • Gopukumar K, Thanawala S, Somepalli V, Rao TSS, Thamatam VB, Chauhan S. 2021. Efficacy and safety of Ashwagandha root extract on cognitive functions in healthy, stressed adults: A randomized, double-blind, placebo-controlled study. Evid Based Compl Alternat Med. 2021: 8254344. doi: 10.1155/2021/8254344.
  • Gorelick J, Rosenberg R, Smotrich A, Hanuš L, Bernstein N. 2015. Hypoglycemic activity of withanolides and elicitated Withania somnifera. Phytochemistry. 116:283–289. doi: 10.1016/j.phytochem.2015.02.029.
  • Groeger AL, Freeman BA. 2010. Signaling actions of electrophiles: anti-inflammatory therapeutic candidates. Mol Interv. 10(1):39–50. doi: 10.1124/mi.10.1.7.
  • Grossman EA, Ward CC, Spradlin JN, Bateman LA, Huffman TR, Miyamoto DK, Kleinman JI, Nomura DK. 2017. Covalent ligand discovery against druggable hotspots targeted by anti-cancer natural products. Cell Chem Biol. 24(11): 1368–1376. e4. doi: 10.1016/j.chembiol.2017.08.013.
  • Gupta P, Goel R, Pathak S, Srivastava A, Singh SP, Sangwan RS, Asif MH, Trivedi PK. 2013. De novo assembly, functional annotation and comparative analysis of Withania somnifera leaf and root transcriptomes to identify putative genes involved in the withanolides biosynthesis. PLoS One. 8(5):e62714. doi: 10.1371/journal.pone.0062714.
  • Gupta S, Bohra M. Sharma K, Kachhwaha S, Kothari S, Jain R. 2021. Leaves and roots of micropropagated plants adopt different pathways for withanolide biosynthesis in Withania coagulans: A comparative transcriptome study. doi: 10.21203/rs.3.rs-299335/v1.[AQ]
  • Gupta SK, Jadhav S, Gohil D, Panigrahi GC, Kaushal RK, Gandhi K, Patil A, Chavan P, Gota V. 2022. Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice. Toxicol Rep. 9: 1204–1212. doi: 10.1016/j.toxrep.2022.05.012.
  • Ha JW, Yu JS, Lee BS, Kang DM, Ahn MJ, Kim JK, Kim KH. 2022. Structural characterization of withanolide glycosides from the roots of Withania somnifera and their potential biological activities. Plants (Basel). 11(6):767. doi: 10.3390/plants11060767.
  • Heyninck K, Lahtela-Kakkonen M, Van der Veken P, Haegeman G, Vanden Berghe W. 2014. Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKβ. Biochem Pharmacol. 91(4):501–509. doi: 10.1016/j.bcp.2014.08.004.
  • Inagaki K, Mori N, Honda Y, Takaki S, Tsuji K, Chayama K. 2017. A case of drug-induced liver injury with prolonged severe intrahepatic cholestasis induced by Ashwagandha. Acta hepatologica Japonica 58: 448–454. doi: 10.2957/kanzo.58.448.
  • Jan R, Asaf S, Numan M, Lubna , Kim K-M. 2021. Plant secondary metabolite biosynthesis and transcriptional regulation in response to biotic and abiotic stress conditions. Agronomy. 11(5):968. doi: 10.3390/agronomy11050968.
  • Kakar SS, Ratajczak MZ, Powell KS, Moghadamfalahi M, Miller DM, Batra SK, Singh SK. 2014. Withaferin A alone and in combination with cisplatin suppresses growth and metastasis of ovarian cancer by targeting putative cancer stem cells. PLoS ONE 9(9): e107596. doi: 10.1371/journal.pone.0107596.
  • Kaushik MK, Kaul SC, Wadhwa R, Yanagisawa M, Urade Y. 2017. Triethylene glycol, an active component of Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction. PLoS One. 12(2):e0172508. doi: 10.1371/journal.pone.0172508.
  • Khanna KL, Schwarting AE, Rother A, Bobbit JM. 1961. Occurrence of tropine and pseudotropine in Withania somnifera. Lloydia. 24: 179–181.
  • Kohnen-Johannsen KL, Kayser O. 2019. Tropane Alkaloids: Chemistry, pharmacology, biosynthesis and production. Molecules. 24(4):796. doi: 10.3390/molecules24040796.
  • Kumar P, Singh R, Nazmi A, Lakhanpal D, Kataria H, Kaur G. 2014. Glioprotective effects of Ashwagandha leaf extract against lead induced toxicity. Biomed Res Int. 2014:182029. doi: 10.1155/2014/182029.
  • Kumar P, Banik SP, Goel A, Chakraborty S, Bagchi M, Bagchi D. 2023. Chemical, microbial and safety profiling of a standardized Withania somnifera (Ashwagandha) extract and withaferin A, a potent novel phytotherapeutic of the millennium. Funct Foods Health Dis. 13(2): 36–51. doi: 10.31989/ffhd.v13i2.1071.
  • Kumar S, Mathew SO, Aharwal RP, Tulli HS, Mohan CD, Sethi G, Ahn KS, Webber K, Sandhu SS, Bishayee A. 2023. Withaferin A: A pleiotropic anticancer agent from the Indian medicinal plant Withania somnifera (L.) Dunal. Pharmaceuticals (Basel). 16(2):160. doi: 10.3390/ph16020160.
  • Kumari M, Gupta RP. 2015. In vitro antibacterial effect of Withania somnifera root extract on Escherichia coli. Vet World. 8(1):57–60. doi: 10.14202/vetworld.2015.57-60.
  • Langade D, Kanchi S, Salve J, Debnath K, Ambegaokar D. 2019. Efficacy and safety of Ashwagandha (Withania somnifera) root extract in insomnia and anxiety: A double-blind, randomized, placebo-controlled study. Cureus. 11(9):e5797. doi: 10.7759/cureus.5797.
  • Lee IC, Choi BY. 2016. Withaferin-A–A natural anticancer agent with pleitropic mechanisms of action. Int J Mol Sci. 17(3):290. doi: 10.3390/ijms17030290.
  • Lin CC, Yang TY, Lu HJ, Wan CK, Hsu SL, Wu CC. 2021. Attenuating role of withaferin A in the proliferation and migration of lung cancer cells via a p53-miR-27a/miR-10b pathway. Oncol. Lett. 21(3):232. doi: 10.3892/ol.2021.12493.
  • Lopresti AL, Smith SJ, Malvi H, Kodgule R. 2019. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine (Baltimore). 98(37): e17186. doi: 10.1097/MD.0000000000017186.
  • Lubarska M, Hałasiński P, Hryhorowicz S, Mahadea DS, Łykowska-Szuber L, Eder P, Dobrowolska A, Krela-Kaźmierczak I. 2023. Liver dangers of herbal products: A case report of Ashwagandha-induced liver injury. Int J Environ Res Public Health. 20(5):3921. doi: 10.3390/ijerph20053921.
  • Mayola E, Gallerne C, Esposti DD, Martel C, Pervaiz S, Larue L, Debuire B, Lemoine A, Brenner C, Lemaire C. 2011. Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2. Apoptosis. 16(10):1014–1027. doi: 10.1007/s10495-011-0625-x.
  • Mikulska P, Malinowska M, Ignacyk M, Szustowski P, Nowak J, Pesta K, Szeląg M, Szklanny D, Judasz E, Kaczmarek G, Ejiohuo OP, Paczkowska-Walendowska M, Gościniak A, Cielecka-Piontek J. 2023. Ashwagandha (Withania somnifera)-current research on the health-promoting activities: A narrative review. Pharmaceutics. 15(4): 1057. doi: 10.3390/pharmaceutics15041057.
  • Ministry of Ayush. 2021. Subject-advisory for refrain from use of Aswagandha (Withania somnifera) leaves. [accessed 2023 June 1]. https://cdn.ayush.gov.in/wp-content/uploads/2021/10/advisory-on-aswagandha.pdf.
  • Modi SJ, Tiwari A, Ghule C, Pawar S, Saste G, Jagtap S, Singh R, Deshmukh A, Girme A, Hingorani L. 2022. Pharmacokinetic study of withanosides and withanolides from Withania somnifera using ultra-high performance liquid chromatography-Tandem mass spectrometry (UHPLC-MS/MS). Molecules. 27(5):1476. doi: 10.3390/molecules27051476.
  • Nagella P, Naik PM, Manohar Sh, Hosakatte NM. 2010. Distribution of withanolide A content in various organs of Withania somnifera (L.) Dunal. Intern J Pharma Bio Sci. 1. ISSN: 0975–6299.
  • Ncube B, Van Staden J. 2015. Tilting plant metabolism for improved metabolite biosynthesis and enhanced human benefit. Molecules. 20(7):12698–12731. doi: 10.3390/molecules200712698.
  • Nile SH, Nile A, Gansukh E, Baskar V, Kai G. 2019. Subcritical water extraction of withanosides and withanolides from Ashwagandha (Withania somnifera L) and their biological activities. Food Chem Toxicol. 132:110659. doi: 10.1016/j.fct.2019.110659.
  • Orrù A, Marchese G, Ruiu S. 2023. Alkaloids in Withania somnifera (L.) Dunal root extract contribute to its anti-inflammatory activity. Pharmacology. 108(3):301–307. doi: 10.1159/000527656.
  • Ozawa M, Morita M, Hirai G, Tamura S, Kawai M, Tsuchiya A, Oonuma K, Maruoka K, Sodeoka M. 2013. Contribution of cage-shaped structure of physalins to their mode of action in inhibition of NF-κB activation. ACS Med Chem Lett. 4(8): 730–735. doi: 10.1021/ml400144e.
  • Pandey SS, Singh S, Pandey H, Srivastava M, Ray T, Soni S, Pandey A, Shanker K, Babu CSV, Banerjee S, Gupta MM, Kalra A. 2018. Endophytes of Withania somnifera modulate in planta content and the site of withanolide biosynthesis. Sci Rep. 8(1):5450. doi: 10.1038/s41598-018-23716-5.
  • Patel SB, Rao NJ, Hingorani LL. 2016. Safety assessment of Withania somnifera extract standardized for withaferin A: Acute and sub-acute toxicity study. J Ayurveda Integr Med. 7(1): 30–37. doi: 10.1016/j.jaim.2015.08.001.
  • Pingali U, Pilli R, Fatima N. 2014. Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy Res. 6(1):12–18. doi: 10.4103/0974-8490.122912.
  • Priyandoko D, Ishii T, Kaul SC, Wadhwa R. 2011. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite. PLoS One. 6(5):e19552. doi: 10.1371/journal.pone.0019552.
  • Rangaraju S, Lokesha AN, Chenna A. 2019. Improved production of withanolides in adventitious root cultures of Withania somnifera by suspension culture method. Biosci Biotech Res Commun. 12(1):73–79. doi: 10.21786/bbrc/12.1/10.
  • Remenapp A, Coyle K, Orange T, Lynch T, Hooper D, Hooper S, Conway K, Hausenblas HA. 2022. Efficacy of Withania somnifera supplementation on adult's cognition and mood. J Ayurveda Integr Med. 13(2):100510. doi: 10.1016/j.jaim.2021.08.003.
  • Rodríguez-Concepción M, Forés O, Martinez-García JF, González V, Phillips MA, Ferrer A, Boronat A. 2004. Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development. Plant Cell. 16(1):144–156. doi: 10.1105/tpc.016204.
  • Sangwan RS, Chaurasiya ND, Lal P, Misra L, Tuli R, and Sangwan NS (2008), Withanolide A is inherently de novo biosynthesized in roots of the medicinal plant Ashwagandha (Withania somnifera). Physiologia Plantarum, 133: 278–287. doi: 10.1111/j.1399-3054.2008.01076.x.
  • Saleem S, Muhammad G, Hussain MA, Altaf M, Bukhari SNA. 2020. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iran J Basic Med Sci. 23(12):1501–1526. doi: 10.22038/IJBMS.2020.44254.
  • Sharma L, Maurya B, Rai SP. 2023. An overview of biotechnological interventions and abiotic elicitors on biomass and withanolide biosynthesis in Withania somnifera (L.) Dunal, Industrial Crops and Products. 193: 116238 doi: 10.1016/j.indcrop.2023.116238.
  • Siddiqui S, Ahmed N, Goswami M, Chakrabarty A, Chowdhury G. 2021. DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha). Curr Res Toxicol. 2: 72–81. doi: 10.1016/j.crtox.2021.02.002.
  • Sikandan A, Shinomiya T, Nagahara Y. 2018. Ashwagandha root extract exerts anti‑inflammatory effects in HaCaT cells by inhibiting the MAPK/NF‑κB pathways and by regulating cytokines. Int J Mol Med. 42(1):425–434. doi: 10.3892/ijmm.2018.3608.
  • Singh M, Poddar NK, Singh D, Agrawal S. 2020. Foliar application of elicitors enhanced the yield of withanolide contents in Withania somnifera (L.) Dunal (variety, Poshita). 3 Biotech. 10(4):157. doi: 10.1007/s13205-020-2153-2.
  • Singh M, Jayant K, Singh D, Bhutani S, Poddar NK, Chaudhary AA, Khan SU, Adnan M, Siddiqui AJ, Hassan MI, Khan FI, Lai D, Khan S. 2022. Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy. Front Cell Infect Microbiol. 12:933824. doi: 10.3389/fcimb.2022.933824.
  • Siriwardane AS, Dharmadasa RM, Samarasinghe K. 2013. Distribution of withaferin A, an anticancer potential agent, in different parts of two varieties of Withania somnifera (L.) Dunal. grown in Sri Lanka. Pak J Biol Sci. 16(3):141–144. doi: 10.3923/pjbs.2013.141.144.
  • Speers AB, Cabey KA, Soumyanath A, Wright KM. 2021. Effects of Withania somnifera (Ashwagandha) on stress and the stress- related neuropsychiatric disorders anxiety, depression, and insomnia. Curr Neuropharmacol. 19(9): 1468–1495. doi: 10.2174/1570159X19666210712151556.
  • Srivastava S, Sanchita , Singh R, Srivastava G, Sharma A. 2018. Comparative study of Withanolide biosynthesis-related miRNAs in root and leaf tissues of Withania somnifera. Appl Biochem Biotechnol. 185(4):1145–1159. doi: 10.1007/s12010-018-2702-x.
  • Sudeep HV, Gouthamchandra K, Shyamprasad K. 2020. Molecular docking analysis of Withaferin A from Withania somnifera with the glucose regulated protein 78 (GRP78) receptor and the SARS-CoV-2 main protease. Bioinformation. 16(5):411–417. doi: 10.6026/97320630016411.
  • Sultana T, Okla MK, Ahmed M, Akhtar N, Al-Hashimi A, Abdelgawad H, Haq IU. 2021. Withaferin A: From ancient remedy to potential drug candidate. Molecules. 26(24):7696. doi: 10.3390/molecules26247696.
  • Tang Q, Ren L, Liu J, Li W, Zheng X, Wang J, Du G. 2020. Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4-ATF3-CHOP axis. Cell Prolif. 53(1):e12706. doi: 10.1111/cpr.12706.
  • Tandon N, Yadav SS. 2020. Safety and clinical effectiveness of Withania somnifera (Linn.) Dunal root in human ailments. J Ethnopharmacol. 255: 112768. doi: 10.1016/j.jep.2020.1.
  • Teoh ES. 2015. Secondary metabolites of plants. Medicinal Orchids of Asia. 59–73. doi: 10.1007/978-3-319-24274-3_5.
  • Tharakan A, Shukla H, Benny IR, Tharakan M, George L, Koshy S. 2021. Immunomodulatory effect of Withania somnifera (Ashwagandha) extract—A randomized, double-blind, placebo controlled trial with an open label extension on healthy participants. J Clin Med. 10(16): 3644. doi: 10.3390/jcm10163644.
  • Thorat SA, Kaniyassery A, Poojari P, Rangel M, Tantry S, Kiran KR, Joshi MB, Rai PS, Botha AM, Muthusamy A. 2022. Differential gene expression and withanolides biosynthesis during in vitro and ex vitro growth of Withania somnifera (L.) Dunal. Front Plant Sci. 13:917770. doi: 10.3389/fpls.2022.917770.
  • Tiwari S, Gupta SK, Pathak AK. 2021. A double-blind, randomized, placebo-controlled trial on the effect of Ashwagandha (Withania somnifera dunal.) root extract in improving cardiorespiratory endurance and recovery in healthy athletic adults. J Ethnopharmacol. 272:113929. doi: 10.1016/j.jep.2021.113929.
  • Tóth M, Benedek AE, Longerich T, Seitz H-K. 2023. Ashwagandha-induced acute liver injury: A case report. Clin Case Rep. 11:e7078. doi: 10.1002/ccr3.7078.
  • Verma N, Gupta SK, Tiwari S, Mishra AK. 2021. Safety of Ashwagandha root extract: A randomized, placebo-controlled, study in healthy volunteers. Complement Ther Med. 57: 102642. doi: 10.1016/j.ctim.2020.102642.
  • Widodo N, Shah N, Priyandoko D, Ishii T, Kaul SC, Wadhwa R. 2009. Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leaves. J Gerontol A Biol Sci Med Sci. 64(10):1031–1038. doi: 10.1093/gerona/glp088.
  • White PT, Subramanian C, Motiwala HF, Cohen MS. 2016. Natural withanolides in the treatment of chronic diseases. Adv Exp Med Biol. 928: 329–373. doi: 10.1007/978-3-319-41334-1_14.
  • Yang J, Yan W, Li Y, Niu L, Ye H, Chen L. 2019. The natural compound withaferin A covalently binds to Cys239 of β-Tubulin to promote tubulin degradation. Mol Pharmacol. 96(6): 711–719. doi: 10.1124/mol.119.117812.
  • Zhang H, Cao CM, Gallagher RJ, Timmermann BN. 2014. Antiproliferative withanolides from several solanaceous species. Nat Prod Res. 28(22): 1941–1951. doi: 10.1080/14786419.2014.919286.
  • Zhao L, Chang WC, Xiao Y, Liu HW, Liu P. 2013. Methylerythritol phosphate pathway of isoprenoid biosynthesis. Annu Rev Biochem. 82:497–530. doi: 10.1146/annurev-biochem-052010-100934.
  • Ziegenfuss TN, Kedia AW, Sandrock JE, Raub BJ, Kerksick CM, Lopez HL. 2018. Effects of an Aqueous extract of Withania somnifera on strength training adaptations and recovery: The STAR trial. Nutrients. 10(11):1807. doi: 10.3390/nu10111807.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.