The Many Faces Of Schisandra, from Detoxification, Lipid Metabolism, and Acetyl-Aldehyde
*This article is not medical advice. Before starting on any health related regimen, seek the advice of your Primary Care Physician or an M.D.
Schisandra
Without a doubt, Schisandra is one my favorite herbs, but it doesn’t mean its right for all situations, but rather specific ones i see often.
Schisandra upregulates ALDH2, the last gene in the pathway to clear Acetyl Aldehyde out of the body. Many of our East Asian friends have significant compromise on this gene, which results in flushing with alcohol consumption.
All About Schisandra In Short:
It supports various functions and mechanisms of action, summarized below:
Lipid Metabolism
Hepatic Anti Oxidant Defense
Detoxification
Bile Acid & Cholesterol Detox Genes
Induces Key CYP3A4 genes - to help with drug metabolism
Transcription Factor Modulation
Acetyl Aldehyde Clearance
Lowers Inflammation and Oxidative Stress Inducing Immune Responses
Improved Mitochondrial Respiration - Complex I
Some “Conditions” Helped By Schisandra
Schisandra is a berry originating in Eastern Asia,and has been shown to increase liver function by increasing enzymatic activity, which in turn increases glutathione production [, 2]. Clinical trials in China by Liu KT in Studies on Fructus Schizandre Cinensis have shown that Schisandra berries can help those with chronic viral hepatitis [3]. One mechanism of hepatitis alleviation is lowering levels of serum glutamic pyruvic transaminase (SGPT), a marker of hepatitis and many other liver disorders [4]. It also may lower SGOT (5). Schisandra is thought to help regrow hepatic cells damaged by alcohol ingestion [6, 7, 8, 9, 10] - and coicidentally Schisandra increases acetyl aldyhde clearnace by upregulating ALDH2. The active parts of Schisandra currently identified as helping liver function are: schizandrin, deoxyschizandrin, gomisins, and pregomisin [11].
Animal studies have shown that Schisandra can increase physical stamina and energy levels [12]. It can also quicken reflexes and increase focus; in addition to protecting against things such as heat shock, frostbite, heavy metal intoxication, radiation, high altitude problems and certain types of inflammation [13]. Schisandra may also be a useful adjunct to chemotherapy due to both its liver protective properties (especially phase 1 detoxification) as well as its immune modulating properties [5]. It can potentially help people handle the toxicity of certain pharmaceuticals they take. Heart contractility has also been shown to increase, without a change in blood pressure [14]. In addition to increasing physical stamina, Schisandra is thought to increase mental stamina and focus as well as visual and hearing acuity [15]. Schisandra is also known to have phytoadaptagenic properties (similar to ginseng) and to assist the endocrine, immune, and sympathetic nervous systems [16]. It may help with cardiovascular and GI problems, increase bile secretion, and even help in the prevention of atherosclerosis [17, 18]. It is also reported that Schisandra has an aphrodisiac affect on both men and women (by increasing men’s staying power and stimulating sensitivity in the females’ genitals) [19].
Schisandra is known to having some antimicrobial functions. It is thought to be especially effective against Bacillus dysenteriae, Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and HIV [20, 21, 22, 23].
In clinical practice it appears to be a very effective antimicrobial against many types of organisms (fungal, bacterial, viral, etc.). It also has been very useful in patients who have suffered from liver stress or need to possibly excrete some stored xenobiotics, chemicals, metals, and mycotoxins. There are quite a few patients who need to be on it for 3-6 months and report many positive changes from taking it. We have seen it help chronic eczema as well.
Chinese medicine typically prescribes Schisandra to treat mental illnesses such as depression, and to help against insomnia [24].
Many studies have demonstrated the anti-inflammatory properties of Schisandra [25, 26]. Also taking Schisandra for 4-6 days decreased hepatic total cholesterol (TC) and triglyceride (TG) levels (by up to 50% and 52%, respectively) in hypercholesterolaemic mice [27]. It also causes relaxation of smooth muscle tissue and prostate tissues and could help with benign prostate hyperplasia [28].
Lipid Metabolism [36,37, 38]
Some of the more impactful effects from Schisandra regarding lipid metabolism are summarized below:
Stimulates PPAR Alpha - master regulator of fatty acid oxidation in the liver
Stimulates CPT1A - increased transport of carnitine
Stimulates ACOX1 - increased mitochondrial peroxisimal and Beta-oxidation
Reduces FASN - Fatty Acid Synthase; reduced de novo lipogensis
Reduces SREBF1 - Lipogensis Transcription Factor
Reduces DGAT2 - Triglyceride synthesis; helps NAFLD
Reduces HMGCR - Lowering cholesterol synthesis
Increases LDLR - increases expression of LDL receptor, increasing LDL clearance
Bile Acid & Cholesterol Detox Genes [36,37]
A summary of the mechanisms that Schisandra effects to improve bile flow, bile acid clearance, and cholesterol excretion:
Induces FXR (Farsenoid X Receptor / NR1H4) - regulates bile acid synthesis, increases BSEP / ABC11 (Bile Salt Export Pump - valve from liver to gallbladder), and lower CYP7A1 (Super Important to Account For)
Lowers CYP7A1 via FXR induction and feedback -
Induces ABCB11 / BSEP - as above, increases bile acid efflux
Increases MRP2 / ABCC2 (Chaperone of toxins into bile after they leave phase 2 conjugation - super important) - increases expression leading to organic anion efflux
Increases SLCO1B1 / SLC O1B3 - hepatic uptake of bile acids and billilrubin, also processes Copoporhyrin I and III.
Liver Anti Oxidant and Cyto Protective Genes - Via NrF2
Increases GCLC / GCLM
Increases SOD1, SOD2
Increases CAT
Increases GPX1/4
Increases PRDX’s - especially PRDX3 in mitochondria
Increases TRNDX’s
Increases HMOX1/2
Increases GSR (Glutathione Recycling; NAD dependent)
Detoxification and Xenobiotic Metabolism Genes
Increases CYP3A4 - strong induction via PXR at 500-1000mg doses of Schisandra extract after one week, inhibition at low infrequent dosing. [29]
Increases CYP2B6 - strong induction via CAR
Increases CYP2C9/19 - Induced
Increases UGT1A1 - decreased activity and expression [31]
Increases UGT1A9/2B7 - Increased activity and expression [31]
Increases GSTP1/A1/M1 - Increased activity and expression via Nrf2 [32]
Increases NQO1 - Increased via Nrf2 [30]
Transcription Factor Modulation
NrF2 - Anti Oxidant Defense and Phase 2 Detox
PPAR Alpha - Fatty Acid Beta Oxidation
PXR (NR1i2) - CYP3A4, UGT Induction [36,37]
CAR (NR1i3) - CYP2B6, UGT Induction
FXR (NR1H4) - bile acid regulation [36,37]
SREBPC1 - lipogenisis expression
Acetyl Aldehyde Clearance
The last gene in the clearance of acetyl aldehyde is ALDH2, cofactors being NAD, Magnesium, Zinc, and Cysteine resides. Inputs into this pathway from gut dysbiosis, fungal overgrowth, candida, alcohol intake, carbohydrates and sugar intake all contribute to acetyl aldehyde formation in addition to histamine! There are important genetic mutations that can significantly downregulate ALDH2, leading to more overload as well. Schisandra mildly stimulates ALDH2 which can help lower acetyl aldehyde levels via NrF2.
Lowers NADPH Oxidase 2
Schisandra has research that shows it inhibits NOX2, one of the key genes implicated in a variety of immune activation oxidative stress inducing cycles - from mast cell activation, to MPO, to prostaglandin synthesis. [33]
Improves Mitochondrial Function
Schisandra has research that shows it increases the activity of Complex I (NADH: Ubiquinone oxioreductase) promoting fasting oxidation of NADH to NAD+. This reduces NADH backlog, raises NAD+, and supports higher ATP production. Its a nice addition to Sirtuin supports, because Sirtuins are NAD+ dependent, and this is especially important inside the mitochondria.
Schisandra also increases the activity of IDH2 (Isocitrate Dehydrogenase), Malic Enzyme 1 and 2, both NADPH generating inside the mitochondria. [34]
Increased Levels of NAD+ Production [35]
Schisandra can help support increasing NAD+ Levels through multiple mechanisms:
Enhanced NADH Oxidation by stimulating Mitochondrial Complex I
Activation of AMPK and PGC-1alpha - increases NAMPT which increases NAD+ biosynthesis and mitochondrial enzymes that consume NADH, thus generating NAD+.
NrF2 Expression - reduce ROS, lowers consumption by PARP
SIRT3 mediated feedback - by raising NAD+ levels, SIRT3 is supported and deacetylates and activates IDH2 and ME2 that improves NADPH and NADH ratios.
Schisandra lignans - upregulate NAMPT , the rate limiting factor in the NAD+ salvage pathway.
Schisandra lowers expression of PARP and CD38 - both of which deplete NAD+
Counter Indications To Give Some Pause
Low NAD, Magnesium or Zinc
Homozygous mutations on CYP7A1 - typically these are the folks with significantly elevated cholesterol [36,37]
Salicylate sensitivity - Schisandra, although not high, does have salicylate content, considerate moderate, so take that into consideration
High Mitochondrial Super Oxide
Blockages at Complex II (SDH) in the electron transport chain
Low dose short term use can significantly inhibit CYP3a4, while chronic moderate dosing can stimulate CYP3a4 [29].
Heme biosynthesis blocks - heme is needed when NrF2 is stimulated
This is a draft of this blog article, more references and additions forthcoming!
References:
1. Cheng, Ni, Naiyan Ren, Hui Gao, Xingsheng Lei, Jianbin Zheng, and Wei Cao. “Antioxidant and Hepatoprotective Effects of Schisandra Chinensis Pollen Extract on CCl4-induced Acute Liver Damage in Mice.” Food and Chemical Toxicology 55 (2013): 234-40. Web.
2. Chiu, P. Y., D. H. Mak, M. K. Poon, and K. M. Ko. “In Vivo Antioxidant Action of a Lignan-Enriched Extract of Schisandra Fruit and an Anthraquinone-Containing Extract of Polygonum Root in Comparison with Schisandrin B and Emodin.” Planta Med Planta Medica 68.11 (2002): 951-56. Web.
3. Liu KT.Studies on fructus Schisandrae chinensis. Annex 12: Studies on fructus Schisandrae chinensis. Plenary lecture, World Health Organization (WHO) Seminar on the Use of Medicinal Plants in Health Care, Sept 1977, Tokyo, Japan. In: WHO Regional Office for the Western Pacific, Final Report, November 1977, Manila, 101–121
4. C. Yank-yong, S. Zeng-Bao, and L. Lian-Niang, “Studies of Fructus schizandrae. IV. Isolation and determination of the active compounds (in lowering high SGPT levels) of Schizandra chinesis Baill,” Scientia Sinica, vol. 19, no. 2, pp. 276-290, 1976.
5. Zhu, M., K.f. Lin, R.y. Yeung, and R.c. Li. “Evaluation of the Protective Effects of Schisandra Chinensis on Phase I Drug Metabolism Using a CCl4 Intoxication Model.” Journal of Ethnopharmacology 67.1 (1999): 61-68. Web.
6. Park, Hyoung Joon, Soo-Jung Lee, Yuno Song, Sun-Hee Jang, Yeoung-Gyu Ko, Suk Nam Kang, Byung Yeoup Chung, Hong-Duck Kim, Gon-Sup Kim, and Jae-Hyeon Cho. “Schisandra Chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats.” Journal of Medicinal Food 17.1 (2014): 103-10. Web.
7. Takeda, Shigefumi, Yoshio Kase, Ichiro Arai, Yasufumi Ohkura, Masayuki Hasegawa, Yuko Sekiguchi, Akemi Tatsugi, Shuji Funo, Masaki Aburada, and Eikichi Hosoya. “Effects of TJN-101, a Lignan Compound Isolated from Schisandra Fruits, on Liver Fibrosis and on Liver Regeneration after Partial Hepatectomy in Rats with Chronic Liver Injury Induced by CCl4.” Folia Pharmacologica Japonica 90.1 (1987): 51-65. Web.
8. Fan, X., Y. Jiang, Y. Wang, H. Tan, H. Zeng, Y. Wang, P. Chen, A. Qu, F. J. Gonzalez, M. Huang, and H. Bi. “Wuzhi Tablet (Schisandra Sphenanthera Extract) Protects against Acetaminophen-Induced Hepatotoxicity by Inhibition of CYP-Mediated Bioactivation and Regulation of NRF2-ARE and P53/p21 Pathways.” Drug Metabolism and Disposition 42.12 (2014): 1982-990. Web.
9. Li, Bin, Lijie Zhu, Ting Wu, Jiachen Zhang, Xinyao Jiao, Xiuying Liu, Yanqun Wang, and Xianjun Meng. “Effects of Triterpenoid From Schisandra Chinensis on Oxidative Stress in Alcohol-Induced Liver Injury in Rats.” Cell Biochemistry and Biophysics Cell Biochem Biophys 71.2 (2014): 803-11. Web.
10. Park, Hyoung Joon, Soo-Jung Lee, Yuno Song, Sun-Hee Jang, Yeoung-Gyu Ko, Suk Nam Kang, Byung Yeoup Chung, Hong-Duck Kim, Gon-Sup Kim, and Jae-Hyeon Cho. “Schisandra Chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats.” Journal of Medicinal Food 17.1 (2014): 103-10. Web.
11. Lu, Yan, and Dao-Feng Chen. “Analysis of Schisandra Chinensis and Schisandra Sphenanthera.” Journal of Chromatography A 1216.11 (2009): 1980-990. Web.
12. Li, T.S.C. 2003. The range of medicinal plants influencing mental and physical performance. In: David H. Watson (ed.) Performance functional foods. Woodhead Publishing Ltd. Cambridge, England. p. 38-60.
13. Panossian, Alexander, and Georg Wikman. “Pharmacology of Schisandra Chinensis Bail.: An Overview of Russian Research and Uses in Medicine.” Journal of Ethnopharmacology 118.2 (2008): 183-212. Web.
14. Li PC, Poon KT, Ko KM (1996). Schisandra chinensis-dependent myocardial protective action of sheng-mai-san in rats. Am. J. Chin. Med., 24: 255-262.
15. Zhukovich, E. N., S. Yu. Bokareva, L. A. Sharikova, T. F. Pribytkova, M. Yu. Semenova, and L. M. Korovina. “Biologically Active Lignans in Extract and Seeds of Schizandra Chinensis.” Pharm Chem J Pharmaceutical Chemistry Journal 41.2 (2007): 94-96. Web.
16. Doncheva, Nina D., Anita St. Mihaylova, and Damianka P. Getova. “Antinociceptive and Anti-inflammatory Effects of Rhodiola Rosea L. Extract in Rats.” Folia Medica 55.3-4 (2013): 70-75. Web.
17. MAEDA, S., TAKEDA, S., MIYAMOTO, Y., ABURADA, M. & HARADA, M. (1985). Effects of gomisin A on liver functions in hepatotoxic chemicals-treated rats. Jpn. J. Pharmacol., 38, 347–353.
18. Park, Ji Young, Hwa Kyoung Shin, You Jin Lee, Young Whan Choi, Sun Sik Bae, and Chi Dae Kim. “The Mechanism of Vasorelaxation Induced by Schisandra Chinensis Extract in Rat Thoracic Aorta.” Journal of Ethnopharmacology 121.1 (2009): 69-73. Web.
19. Kim, Hye Kyung, Yun Ok Bak, Bo Ram Choi, Chen Zhao, Hee Ju Lee, Chul Young Kim, Sung Won Lee, Ju Hong Jeon, and Jong Kwan Park. “The Role of the Lignan Constituents in the Effect of Schisandra Chinensis Fruit Extract on Penile Erection.” Phytotherapy Research Phytother. Res. 25.12 (2011): 1776-782. Web.
20. Mulyaningsih, Sri, Mahmoud Youns, Mahmoud Z. El-Readi, Mohamed L. Ashour, Endalkachew Nibret, Frank Sporer, Florian Herrmann, Jürgen Reichling, and Michael Wink. “Biological Activity of the Essential Oil of Kadsura Longipedunculata (Schisandraceae) and Its Major Components.” Journal of Pharmacy and Pharmacology 62.8 (2010): 1037-044. Web.
21. Jinghao, Zhang, Xiao Mingxia, and Ji Ping. “Experimental Study on Bacteriostasis of Scutellaria,Coptis and Schisandra on Five Kinds of Multi-drug Resistant Bacteria.” Xinjiang Medical Journal (2012): n. pag. Web.
22. Chen, Xiaoqiang, Ying Zhan, and Yuangang Zu. “Composition and Biological Activities of the Essential Oil from Schisandra Chinensis Obtained by Solvent-free Microwave Extraction.” LWT - Food Science and Technology 44.10 (2011): 2047-052. Web.
23. Li, Rong-Tao, and Et Al. Et Al. “Lancifodilactone G: A Unique Nortriterpenoid Isolated from Schisandra Lancifolia and Its Anti-HIV Activity.” ChemInform 36.42 (2005): n. pag. Web.
24. Zhang, Chenning, Xin Mao, Xu Zhao, Zhi Liu, Bing Liu, Huan Li, Kaishun Bi, and Ying Jia. “Gomisin N Isolated from Schisandra Chinensis Augments Pentobarbital-induced Sleep Behaviors through the Modification of the Serotonergic and GABAergic System.” Fitoterapia 96 (2014): 123-30. Web.
25. Qiao, Wei, Chuan Zhao, Nan Qin, Hui Yuan Zhai, and Hong Quan Duan. “Identification of Trans-tiliroside as Active Principle with Anti-hyperglycemic, Anti-hyperlipidemic and Antioxidant Effects from Potentilla Chinesis.” Journal of Ethnopharmacology 135.2 (2011): 515-21. Web.
26. Kang, Saeromi, Kyoung-Pil Lee, Soo-Jin Park, Dae-Young Noh, Jung-Min Kim, Hyung Ryong Moon, Young-Geun Lee, Young-Whan Choi, and Dong-Soon Im. “Identification of a Novel Anti-inflammatory Compound, α-cubebenoate from Schisandra Chinensis.” Journal of Ethnopharmacology 153.1 (2014): 242-49. Web.
27. Pan, Si-Yuan, Hang Dong, Xing-Ye Zhao, Chun-Jing Xiang, Hai-Yan Fang, Wang-Fun Fong, Zhi-Ling Yu, and Kam-Ming Ko. “Schisandrin B from Schisandra Chinensis Reduces Hepatic Lipid Contents in Hypercholesterolaemic Mice.” Journal of Pharmacy and Pharmacology 60.3 (2008): 399-403. Web.
28. Choo, Seol Ho, Hyun Hwan Sung, Mee Ree Chae, Su Jeong Kang, Deok Hyun Han, Jong Kwan Park, Insuk So, and Sung Won Lee. “Effects of Schisandra Chinensis Extract on the Relaxation of Isolated Human Prostate Tissue and Smooth Muscle Cell.” Journal of Ethnopharmacology 156 (2014): 271-76. Web.29. A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities. Feng Zhang, et. al. REVIEW article. Front. Pharmacol., 10 March 2022. Sec. Drug Metabolism and Transport. Volume 13 - 2022 | https://doi.org/10.3389/fphar.2022.81603630. Schisandrin A regulates the Nrf2 signaling pathway and inhibits NLRP3 inflammasome activation to interfere with pyroptosis in a mouse model of COPDJiamin Zeng et. al. Eur J Med Research. 2023 Jul 3;28(1):217. doi: 10.1186/s40001-023-01190-8.PMID: 37400851. PMCID: PMC10316617. DOI: 10.1186/s40001-023-01190-8. 31. Inhibition of UDP-Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis. Jin-Hui Song et. al. Phytother Res. 2015 Jun 18;29(10):1658–1664. doi: 10.1002/ptr.5395. PMCID: PMC6594156 NIHMSID: NIHMS1036970 PMID: 26084208Phytother Research. PMC: 2019 Jun 26.32. Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway. Jin-Lian He, et. al. Drug Des Devel Therapy. . 2014 Dec 17;9:127–146. doi: 10.2147/DDDT.S68501. PMCID: PMC4277124 PMID: 2555290233. Lignans with NADPH Oxidase 2 (NOX2)-inhibitory Activity from the Fruits of Schisandra chinensis. By Jung-Min Park et. al. College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of KoreaNatural Product Sciences. 24(1) : 59-65 (2018). https://doi.org/10.20307/nps.2018.24.1.59. 34. Schisandra Extract and Ascorbic Acid Synergistically Enhance Cognition in Mice Through Modulation of Mitochondrial Respiration. Yunseon Jang. Nutrients. 2020 Mar 25;12(4):897. doi: 10.3390/nu12040897. PMID: 32218327. PMCID: PMC7230947. DOI: 10.3390/nu1204089735. Identification of components that increase NAD+ levels in oxygen-glucose deprived HUVEC s from Schisandra chinensis (Turcz.) Baill. Based on spectrum-effect correlation analysis and target cell extraction. By Liwenyu Chen, et. al. Fitoterapia. . 2025 Mar:181:106347. doi: 10.1016/j.fitote.2024.106347. Epub 2024 Dec 17. PMID: 39701499. DOI: 10.1016/j.fitote.2024.10634736. A comprehensive review of Schisandra chinensis lignans: pharmacokinetics, pharmacological mechanisms, and future prospects in disease prevention and treatmentDanushiya Ehambarampillai , et. al. China Medicine. . 2025 Apr 9;20:47. doi: 10.1186/s13020-025-01096-z. PMCID: PMC11984061 PMID: 4020541237. Schisandra chinensis in Liver Disease: Exploring the Mechanisms and Therapeutic Promise of an Ancient Chinese Botanical. By Tamer A. Addissouky et. al. Archives of Pharmacology and Therapeutics. Scientific Archives. Volume 6 | Issue 1 | DOI: https://doi.org/10.33696/Pharmacol.6.05238. Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice. By Chun-Mei Wang, et. al. Lipids in Health and Disease volume 15, Article number: 195 (2016)