Life Extension Magazine®

Physician holding a healthy hologram liver boosted by cucumis melo extract

Fight Oxidative Liver Damage

Up to 100% of overweight and obese individuals suffer the silent affliction of nonalcoholic fatty liver disease, or NAFLD, in which oxidized liver tissue turns rancid. A synergistic combination of the adaptogen Schisandra chinensis and a patented extract of the melon Cucumis melo has been shown to offer unique protection against the mitochondrial oxidant damage that triggers NAFLD.

Scientifically reviewed by: Dr. Crystal M. Gossard, DCN, CNS, LDN, in October 2024. Written by: Kirk Stokel.

Novel Method to Effectively Combat Oxidative Liver Damage

Little known to the general public is the silent epidemic of non-alcoholic fatty liver disease or NAFLD, which afflicts up to 40% of all Americans.1 NAFLD particularly targets those who carry around excess weight. For the nearly 70% of Americans who are overweight or obese,2 that figure rises to a shocking 50-100%.3,4

Ominously, NAFLD sets the stage for a progression of lethal diseases that can include cancer, atherosclerosis, and diabetes.5,6 Risk of death from all causes skyrockets more than four-fold in NAFLD sufferers - and more than eight-fold for early cardiac death.7

Because of both physician and patient ignorance, most victims of NAFLD are entirely unaware they have it.

No drug can halt this widespread disease's potentially lethal progress.3

The exciting news is scientists have recently identified a novel intervention to halt two of NAFLD's core pathologic processes - lipid peroxidation, wherein excess liver fat turns rancid under continuous assault from free radicals, and rampant oxidative damage from disease-induced mitochondrial dysfunction.

In this article, you will discover how a beneficial adaptogen called Schisandra chinensis and a patented proprietary extract of the melon Cucumis melo work in synergy to restore vital antioxidant functions typically depleted in NAFLD patients.

Rancid Fat and Mitochondrial Decay

NAFLD (non-alcoholic fatty liver disease) has been called a disease of modern living.

It is a direct consequence of the typical American sedentary lifestyle and a diet rich in sugar and saturated fats.8

Inactivity, overconsumption, and emotional stress result in a spiral that starts with overweight and obesity and culminates in metabolic syndrome, a cluster of deadly fat- and sugar-related physiological and metabolic derangements that range from hypertension to type 2 diabetes.

NAFLD is now widely recognized as the liver's manifestation of metabolic syndrome.8 It begins with accumulation of excessive amounts of liver fat in the form of triglycerides.9 Fat is highly vulnerable to oxidative damage, and massive oxidative stress is the next step in development of NAFLD, in the process known as lipid peroxidation.8,10

Restoring Youthful Liver Defense Mechanisms

When we are young, we're protected against this deadly cascade of events by two complementary mechanisms.

In the first, a liver enzyme called superoxide dismutase, or SOD, converts highly reactive free oxygen radicals into hydrogen peroxide.11 That delays but doesn't end the threat of lipid peroxidation, because hydrogen peroxide itself generates new free radicals of its own.

To fully quench the free radical threat, a second set of antioxidant enzymes is recruited: catalase and glutathione peroxidase, which act on hydrogen peroxide and quickly convert it into harmless water molecules.12,13

The extraordinary oxidative stress inflicted on the liver in NAFLD, however, puts all of these protective enzyme systems into overdrive. Early in the disease, their activity is ramped up substantially in an effort to compensate - but eventually they become depleted and burn out.14-17

As the body loses its natural primary antioxidant mechanisms, it accumulates lipid peroxidation products, and liver mitochondria begin to fail. This makes people increasingly vulnerable to non-alcoholic steatohepatitis, cirrhosis, fibrosis, liver cancer, and cardiovascular diseases.10,18

Supporting the liver's mitochondrial antioxidant enzyme systems is a vital step in preventing the consequences of NAFLD. As you will now see, the synergistic action of Schisandra chinensis and Cucumis melo directly replenish essential SOD, while at the same time stimulating glutathione peroxidase, effectively targeting lipid peroxidation and mitochondrial dysfunction in the liver.

Optimizing Liver Mitochondrial Function and Antioxidant Defense

Purified extract from a non-GMO Cucumis melo melon has been found to be rich in superoxide dismutase (SOD), the first enzyme in your body's mitochondrial oxidant protection system.19,20 Melon-derived SOD quickly converts primary free oxygen radicals into hydrogen peroxide.

That hydrogen peroxide must be rapidly converted into water to complete the mitochondrial oxidant detoxification process. That task is handled by a second liver-protective agent, an extract of the Chinese vine Schisandra chinensis.

Schisandra extract complements the melon extract by stimulating the liver mitochondrial antioxidant enzyme, glutathione peroxidase, that converts hydrogen peroxide to water.21-24

In the presence of both adequate SOD and enhanced glutathione peroxidase activity, mitochondria can readily convert deadly reactive oxygen species first to hydrogen peroxide and then to harmless water.

Now let's examine the data on just how well each component works to protect your body from the punishing effects of NAFLD.

Synergistic Liver Disease and Oxidative Stress Defense

Melon extracts supply important antioxidant SOD enzymes to SOD-depleted liver tissues in NAFLD. Studies reveal that supplementation with specially coated melon extracts directly prevents lipid peroxidation damage to liver and other tissues.19,25-27

But melon extracts rich in SOD have much more profound effects that can protect your liver, not only from oxidant stress, but also directly from the effects of overweight and obesity.

Animals fed high-fat diets develop the metabolic syndrome, just as humans do. But when supplemented with melon extract, hamsters with metabolic syndrome experienced a 68% drop in triglyceride levels, a 12% drop in liver primary free radicals, a 35% drop in lipid and protein oxidation, and a massive 99% drop in levels of the inflammatory fat-derived cytokine leptin.28 These effects led to a 39% reduction in insulin levels, a 41% reduction in insulin resistance, and a 25% reduction in detrimental belly fat accumulation. Supplemented animals also exhibited a 73% reduction in liver fat infiltration and were completely protected against progression of NAFLD to non-alcoholic steatohepatitis. Non-alcoholic steatohepatitis or NASH is an advanced form of fatty liver disease developed in the absence of alcohol abuse that can progress to scarring of the liver, which may lead to cirrhosis.

Novel Method to Combat Widespread Liver Damage

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Americans, reaching a prevalence of up to 100% in overweight and obese individuals.
NAFLD is caused by oxidative damage to excessive fat stores in the process called lipid peroxidation, in which liver tissue turns rancid.
No drug exists to prevent or reverse NAFLD.
A synergistic combination of Schisandra chinensis and a patented proprietary extract of the melon Cucumis melo have been shown to provide unique protection against the mitochondrial oxidant damage that triggers NAFLD.

An intriguing finding just published in mid-2011 is that melon extracts' SOD-boosting effects reduce production of stress proteins in animal studies.29 These proteins are a direct measure of the impact of stress on organs and tissues. Stress and the stress hormone cortisol are known to be contributors to development of NAFLD.30 And severe emotional or occupational stress triggers oxidant damage and inflammation.31,32 Those facts inspired scientists to determine whether melon extracts might ameliorate stress and fatigue in human subjects, making them less vulnerable to NAFLD.

Seventy healthy volunteers, aged 30-55 who experienced daily stress and fatigue, took 10 mg per day of proprietary melon extract or a placebo for 4 weeks.33 Supplemented patients experienced significantly reduced stress and fatigue, and improved physical, cognitive, and behavioral performance, compared with placebo recipients. They also enjoyed significant improvements in quality of life and perceived stress, while there were no adverse effects at any point in the study.

Schisandra chinensis extract complements SOD activity, stimulating glutathione peroxidase enzymatic activity to optimize liver protection.

Schisandra extract has been known to protect liver function for more than 4 decades,34 but it's only recently that we've learned that it does so specifically by boosting mitochondrial antioxidant function.35 In that fashion, the extract confers powerful protection against a host of oxidative liver toxins (including mercury).35-42 Rates of lipid peroxidation, the deadly first consequence of liver fat accumulation in NAFLD, are markedly reduced following supplementation with schisandra extract.43-45 The result: dramatic reductions in liver cell death and fibrosis.46

Schisandra extract is so powerful at mitigating mitochondrial oxidant stress in liver cells that it delays aging in the face of experimentally induced oxidant stress.47 Aging mice demonstrate progressively worsening impairment in mitochondrial oxidant status, resulting in decreased mitochondrial energy production and early death.48 But long-term supplementation with schisandra extract reversed those trends, suppressed mitochondrial ROS production, enhanced mitochondrial energy output, and ultimately improved survival, compared with control animals.48

Schisandra extract is especially notable for its effects on liver fat accumulation in diabetics,49 a group at extremely high risk (virtually 100%) for developing NAFLD.50 Diabetic rats' livers are severely depleted in glutathione, a natural antioxidant. But schisandra supplementation improved glutathione status in liver cells, thanks to its stimulation of glutathione peroxidase enzymes, and prevented oxidant induced liver damage.51 A subsequent study showed that even in non-diabetic animals with experimentally induced NAFLD, schisandra extract decreased liver total cholesterol by 50% and triglycerides by 52% - effects similar to those produced by the prescription drug fenofibrate.52

Human studies are no less encouraging. An open trial in 56 patients with acute or chronic hepatitis, cirrhosis, or fatty liver (steatosis) using 22.5 mg per day of schisandrins demonstrated decreased serum markers of liver cell injury, even in patients with cirrhosis, normally considered an irreversible condition.53 A placebo-controlled study of the same extract formulation in patients with chronic hepatitis (a condition that imposes extreme oxidant stress on liver tissue) demonstrated significant decreases in liver damage markers after just one week.53 Neither study detected any side effects of the extract.

Schisandra extract's ability to protect liver cells from lipid peroxidation offers protection beyond NAFLD-related damage. Studies show that the extract protects against drug-related liver damage as well; that's of critical importance in many conditions in which drug dosing is limited by liver toxicity. Schisandrin B, a major schisandra component, protects liver tissue against toxicity induced by tacrine (Cognex®), a drug that was commonly used to treat Alzheimer's disease - and it independently improves cognitive function.54

The Deadly Impact of Excessive Liver Fat

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Americans and has become a major public health problem.9,55 Sedentary, overweight people, particularly those with other early indications of the metabolic syndrome, are at risk for the progression of NAFLD to a series of increasingly devastating consequences.55

The first of these consequences is called non- alcoholic steatohepatitis, or NASH. Roughly 15-30% of people with NAFLD will go on to have NASH.3 NASH is associated with a massive outpouring of inflammatory cytokines in the liver, which eventually lead to the toughened, scarred liver seen in cirrhosis.56

Cirrhosis, in turn, causes rapid and irreversible loss of liver function at a rate of 3-4% per year.55 And NASH-related cirrhosis is also a major risk factor for liver cancer.

Excessive liver fat in NAFLD is also directly associated with increased risks of developing diabetes, hypertension, abnormal EKG findings, and the endothelial dysfunction that leads to heart attacks and strokes.55

Once NAFLD is fully developed, this deadly progression of events is nearly impossible to reverse - but NAFLD itself is a preventable condition, given proper attention to diet, exercise, and appropriate supplementation.8 While no prescription drug has any impact on NAFLD, natural products that target mitochondria offer considerable potential for controlling the oxidative stress associated with NAFLD.8

If you can prevent NAFLD, you can prevent its consequences. And if you can do that, you can prevent early death.

Melon Extract Formulation Delivers Intact SOD Enzymes

Delivering whole enzymes via the oral route is difficult because they are large protein molecules readily degraded in the stomach. The SOD enzyme in the melon extract is just such a large protein, so the developers had to find a way to prevent that degradation.25

Their solution was to encapsulate the SOD enzymes in a protective sheath of organic material that allows the enzyme to pass unscathed through the stomach into the intestine, where it can be maximally absorbed.25 Studies show that this melon concentrate, given orally, results in significant increases in plasma SOD levels after just 12 days.29

The schisandra extract requires no special packaging, because its active components are small biological molecules readily absorbed in all segments of the intestine.59 They act by stimulating glutathione peroxidase enzyme activity in mitochondria, not by physically replenishing antioxidant enzymes as the melon extract does with SOD.21-25

Summary

The epidemic of obesity and the metabolic syndrome brings with it a nearly universal risk of serious liver damage in the form of non-alcoholic fatty liver disease, or NAFLD.

A large proportion of people with NAFLD goes on to suffer liver failure, cardiovascular disease, and is at increased risk for liver cancer. No drug is available to treat or prevent NAFLD, and Americans' sedentary lifestyle and unhealthy eating habits continue to promote the disease.

Because NAFLD is the direct result of oxidant stress acting on excessive accumulations of liver fat, however, it is amenable to treatment, and even prevention, by powerful nutraceuticals that restore liver antioxidant function to youthful levels.

A pair of fruit extracts (from melons and the Chinese "five flavor berry") acts as a collaborative superfood combination that detoxifies primary free radicals and converts them to harmless water.

Understanding Lipid Peroxidation

If you've ever smelled a stick of butter or a piece of cheese that's gone rancid, that is the result of lipid peroxidation. That's exactly what is going on in your liver as NAFLD progresses - your liver is literally turning rancid.

Here's what's happening in your liver during lipid peroxidation.

Free radicals, or reactive oxygen species (ROS), are natural byproducts of daily biological processes including cellular respiration and energy production. These processes occur in the tiny organelles called mitochondria. That makes mitochondria both the principle producers and primary targets of free radical - induced oxidant stress.

Liver cells are rich in mitochondria because of their enormous metabolic burden. As liver cells age and their mitochondria suffer free radical attack, their membranes become damaged, which leads to formation of additional reactive molecules often termed "secondary" free radicals.58,59 These secondary free radicals trigger a vicious and deadly cycle of lipid peroxidation, membrane damage, impaired mitochondrial function, and further free radical generation.58,60

Liver cells with impaired mitochondrial function can't survive and quickly fall victim to inflammation and cell death.61 As liver cells die off, they are replaced by the scar tissue of cirrhosis and ultimately liver fibrosis.62 A once vibrant and metabolically active organ gradually becomes a massive "dead zone," incapable of performing the myriad functions of a healthy liver and vulnerable to the DNA damage that leads ultimately to cancer.61

This progression from NAFLD to liver failure is a hallmark of modern-day aging.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

Editor's Note

Science continues to evolve, and new research is published daily. As such, we have a more recent article on this topic: Protect Against Fatty Liver with Targeted Probiotics

References

1. Amarapurkar D, Kamani P, Patel N, et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol. 2007 Jul-Sep;6(3):161-3.

2. Available at: http://www.cdc.gov/nchs/fastats/overwt.htm. Accessed September 16, 2011.

3. Koek GH. Treatment of non-alcoholic fatty liver disease. Ned Tijdschr Geneeskd. 2011;155:A3181.

4. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85.

5. Wong VW, Wong GL, Yip GW, et al. Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut. 2011 May 20.

6. Smith BW, Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol. 2011 May 10;7(8):456-65.

7. Dunn W, Xu R, Wingard DL, et al. Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol. 2008 Sep;103(9):2263-71.

8. McCarty MF. Full-spectrum antioxidant therapy featuring astaxanthin coupled with lipoprivic strategies and salsalate for management of non-alcoholic fatty liver disease. Med Hypotheses. 2011 Oct;77(4):550-6.

9. Krawczyk M, Bonfrate L, Portincasa P. Nonalcoholic fatty liver disease. Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):695-708.

10. Machado MV, Ravasco P, Jesus L, et al. Blood oxidative stress markers in non-alcoholic steatohepatitis and how it correlates with diet. Scand J Gastroenterol. 2008 Jan;43(1):95-102.

11. MacMillan-Crow LA, Crow JP. Does more MnSOD mean more hydrogen peroxide? Anticancer Agents Med Chem. 2011 Feb;11(2):178-80.

12. Kirova Iu I, Borodulin VB. Biochemical basis of the single theory of aging. Part II. The cell aerobic status, the hypoxia resistance and proliferation. Adv Gerontol. 2009;22(1):74-83.

13. Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: From molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2011 Oct 1;15(7);1957-97.

14. Saricam T, Kircali B, Koken T. Assessment of lipid peroxidation and antioxidant capacity in non-alcoholic fatty liver disease. Turk J Gastroenterol. 2005 Jun;16(2):65-70.

15. Perlemuter G, Davit-Spraul A, Cosson C, et al. Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease. Liver Int. 2005:Oct;25(5):946-53.

16. Yesilova Z, Yaman H, Oktenli C, et al. Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2005 Apr;100(4):850-5.

17. Kohjima M, Enjoji M, Higuchi N, et al. Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med. 2007 Sep;20(3):351-8.

18. Madan K, Bhardwaj P, Thareja S, Gupta SD, Saraya A. Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD). J Clin Gastroenterol. 2006 Nov-Dec;40(10):930-5.

19. Vouldoukis I, Lacan D, Kamate C, et al. Antioxidant and anti-inflammatory properties of a Cucumis melo LC. extract rich in superoxide dismutase activity. J Ethnopharmacol. 2004 Sep;94(1):67-75.

20. Lester GE, Jifon JL, Crosby KM. Superoxide dismutase activity in mesocarp tissue from divergent Cucumis melo L. genotypes. Plant Foods Hum Nutr. 2009 Sep;64(3):205-11.

21. Chen N, Ko M. Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts. Biol Pharm Bull. 2010;33(5):825-9.

22. Ip SP, Poon MK, Che CT, Ng KH, Kong YC, Ko KM. Schisandrin B protects against carbon tetrachloride toxicity by enhancing the mitochondrial glutathione redox status in mouse liver. Free Radic Biol Med. 1996;21(5):709-12.

23. Chang HF, Lin YH, Chu CC, Wu SJ, Tsai YH, Chao JC. Protective effects of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract on liver injury in rats. Am J Chin Med. 2007;35(6):995-1009.

24. Yan F, Zhang QY, Jiao L, et al. Synergistic hepatoprotective effect of Schisandrae lignans with Astragalus polysaccharides on chronic liver injury in rats. Phytomedicine. 2009 Sep;16(9):805-13.

25. Vouldoukis I, Conti M, Krauss P, et al. Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Phytother Res. 2004 Dec;18(12):957-62.

26. Kick J, Hauser B, Bracht H, et al. Effects of a cantaloupe melon extract/wheat gliadin biopolymer during aortic cross-clamping. Intensive Care Med. 2007 Apr;33(4):694-702.

27. Muth CM, Glenz Y, Klaus M, Radermacher P, Speit G, Leverve X. Influence of an orally effective SOD on hyperbaric oxygen-related cell damage. Free Radic Res. 2004 Sep;38(9):927-32.

28. Decorde K, Agne A, Lacan D, et al. Preventive effect of a melon extract rich in superoxide scavenging activity on abdominal and liver fat and adipokine imbalance in high-fat-fed hamsters. J Agric Food Chem. 2009 Jul 22;57(14):6461-7.

29. Lalles JP, Lacan D, David JC. A melon pulp concentrate rich in superoxide dismutase reduces stress proteins along the gastrointestinal tract of pigs. Nutrition. 2011 Mar;27(3):358-63.

30. Targher G, Bertolini L, Rodella S, Zoppini G, Zenari L, Falezza G. Associations between liver histology and cortisol secretion in subjects with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2006 Mar;64(3):337-41.

31. Grossi G, Perski A, Evengard B, Blomkvist V, Orth-Gomer K. Physiological correlates of burnout among women. J Psychosom Res. 2003 Oct;55(4):309-16.

32. Casado A, De Lucas N, Lopez-Fernandez E, Sanchez A, Jimenez JA. Lipid peroxidation, occupational stress and aging in workers of a prehospital emergency service. Eur J Emerg Med. 2006 Jun;13(3):165-71.

33. Milesi MA, Lacan D, Brosse H, Desor D, Notin C. Effect of an oral supplementation with a proprietary melon juice concentrate (Extramel) on stress and fatigue in healthy people: a pilot, double-blind, placebo-controlled clinical trial. Nutr J. 2009;8:40.

34. Li XY. Bioactivity of neolignans from fructus Schizandrae. Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:31-7.

35. Lam PY, Chiu PY, Leung HY, Chen N, Leong PK, Ko KM. Schisandrin B co-treatment ameliorates the impairment on mitochondrial antioxidant status in various tissues of long-term ethanol treated rats. Fitoterapia. 2010 Dec;81(8):1239-45.

36. Kim SH, Kim YS, Kang SS, Bae K, Hung TM, Lee SM. Anti-apoptotic and hepatoprotective effects of gomisin A on fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide in mice. J Pharmacol Sci. 2008 Feb;106(2):225-33.

37. Ip SP, Yiu HY, Ko KM. Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity. Mol Cell Biochem. 2000 May;208(1-2):151-5.

38. Ko KM, Ip SP, Poon MK, et al. Effect of a lignan-enriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity. Planta Med. 1995 Apr;61(2):134-7.

39. Ip SP, Ko KM. The crucial antioxidant action of schisandrin B in protecting against carbon tetrachloride hepatotoxicity in mice: a comparative study with butylated hydroxytoluene. Biochem Pharmacol. 1996 Dec 13;52(11):1687-93.

40. Ip SP, Mak DH, Li PC, Poon MK, Ko KM. Effect of a lignan-enriched extract of Schisandra chinensis on aflatoxin B1 and cadmium chloride-induced hepatotoxicity in rats. Pharmacol Toxicol. 1996 Jun;78(6):413-6.

41. Zhu M, Lin KF, Yeung RY, Li RC. Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model. J Ethnopharmacol. 1999 Oct;67(1):61-8.

42. Stacchiotti A, Li Volti G, Lavazza A, Rezzani R, Rodella LF. Schisandrin B stimulates a cytoprotective response in rat liver exposed to mercuric chloride. Food Chem Toxicol. 2009 Nov;47(11):2834-40.

43. Zhang TM, Wang BE, Liu GT. Effect of schisandrin B on lipoperoxidative damage to plasma membrane of rat liver in vitro. Zhongguo Yao Li Xue Bao. 1992 May;13(3):255-8.

44. Zhang TM, Wang BE, Liu GT. Action of schizandrin B, an antioxidant, on lipid peroxidation in primary cultured hepatocytes. Zhongguo Yao Li Xue Bao. 1989 Jul;10(4):353-6.

45. Lu H, Liu GT. Anti-oxidant activity of dibenzocyclooctene lignans isolated from Schisandraceae. Planta Med. 1992 Aug;58(4):311-3.

46. Takeda S, Kase Y, Arai I, et al. 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. Nihon Yakurigaku Zasshi. 1987 Jul;90(1):51-65.

47. Chiu PY, Leung HY, Poon MK, Ko KM. Chronic schisandrin B treatment improves mitochondrial antioxidant status and tissue heat shock protein production in various tissues of young adult and middle-aged rats. Biogerontology. 2006 Aug;7(4):199-210.

48. Ko KM, Chen N, Leung HY, Leong EP, Poon MK, Chiu PY. Long-term schisandrin B treatment mitigates age-related impairments in mitochondrial antioxidant status and functional ability in various tissues, and improves the survival of aging C57BL/6J mice. Biofactors. 2008;34(4):331-42.

49. Opletal L, Krenková M, Havlícková P. Phytotherapeutic aspects of diseases of the circulatory system. 8. Chinese magnolia (Schisandra chinensis (Turcz.) Baill.): production of the drugs and their evaluation, therapeutic and dietary preparations. Ceska Slov Farm. 2001 Sep;50(5):219-24.

50. Smith BW, Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol. 2011 May 10;7(8):456-65.

51. Mak DH, Ko KM. Alterations in susceptibility to carbon tetrachloride toxicity and hepatic antioxidant/detoxification system in streptozotocin-induced short-term diabetic rats: effects of insulin and Schisandrin B treatment. Mol Cell Biochem. 1997 Oct;175(1-2):225-32.

52. Pan SY, Dong H, Zhao XY, et al. Schisandrin B from Schisandra chinensis reduces hepatic lipid contents in hypercholesterolaemic mice. J Pharm Pharmacol. 2008 Mar;60(3):399-403.

53. Akbar N, Tahir RA, Santoso WD, et al. Effectiveness of the analogue of natural Schisandrin C (HpPro) in treatment of liver diseases: an experience in Indonesian patients. Chin Med J (Engl). 1998 Mar;111(3):248-51.

54. Pan SY, Han YF, Carlier PR, et al. Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice. Planta Med. 2002 Mar;68(3):217-20.

55. Sanyal AJ. NASH: A global health problem. Hepatol Res. 2011 Jul;41(7):670-4.

56. Koek GH, Liedorp PR, Bast A. The role of oxidative stress in non-alcoholic steatohepatitis. Clin Chim Acta. 2011 Jul 15;412(15-16):1297-305.

57. Chen XM, Li JS, Li W, et al. Intestinal absorption of the effective components of Schisandra chinensis Baill by rats single-pass perfusion in situ. Yao Xue Xue Bao. 2010 May;45(5):652-8.

58. Pessayre D, Berson A, Fromenty B, Mansouri A. Mitochondria in steatohepatitis. Semin Liver Dis. 2001;21(1):57-69.

59. Rector RS, Thyfault JP, Uptergrove GM, et al. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J Hepatol. 2010 May;52(5):727-36.

60. Serviddio G, Bellanti F, Vendemiale G, Altomare E. Mitochondrial dysfunction in nonalcoholic steatohepatitis. Expert Rev Gastroenterol Hepatol. 2011 Apr;5(2):233-44.

61. Gambino R, Musso G, Cassader M. Redox balance in the pathogenesis of nonalcoholic Fatty liver disease: mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2011 Sep 1;15(5):1325-65.

62. Das KS, Balakrishnan V, Mukherjee S, Vasudevan DM. Evaluation of blood oxidative stress-related parameters in alcoholic liver disease and non-alcoholic fatty liver disease. Scand J Clin Lab Invest. 2008;68(4):323-34.