Garcinia cambogia, Either Alone or in Combination With Green Tea, Causes Moderate to Severe Liver Injury.

BACKGROUND & AIMS: Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G cambogia have been reported, but its role in liver injury is controversial. METHODS: Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G cambogia either alone (n = 5) or in combination with green tea (n = 16) or Ashwagandha (n = 1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G cambogia and 103 patients from other HDS. RESULTS: Patients who took G cambogia were between 17 and 54 years, with liver injury arising 13-223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G cambogia group (P < .018), the median time for improvement in total bilirubin was significantly lower compared with the control groups (10 vs 17 and 13 days; P = .03). The presence of HLA-B∗35:01 allele was significantly higher in the G cambogia containing HDS (55%) compared with patients because of other HDS (19%) (P = .002) and those with acute liver injury from conventional drugs (12%) (P = 2.55 × 10-6). CONCLUSIONS: The liver injury caused by G cambogia and green tea is clinically indistinguishable. The possible association with HLA-B∗35:01 allele suggests an immune-mediated mechanism of injury. CLINICAL TRIALS: gov number: NCT00345930.

HLA-B*35:01 and Green Tea-Induced Liver Injury.

BACKGROUND AND AIMS: Herbal supplements, and particularly multi-ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea-associated liver injury. APPROACH AND RESULTS: Among 1,414 patients enrolled in the U.S. Drug-Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15-448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% confidence interval [CI], 58-87) of green tea cases, but only 15% (95% CI, 10-20) caused by other supplements and 12% (95% CI, 10-14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5-11.5). CONCLUSIONS: Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01, suggesting that it is idiosyncratic and immune mediated.

Exogenous GDF11 attenuates non-canonical TGF-ß signaling to protect the heart from acute myocardial ischemia-reperfusion injury.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta 1 (TGF-ß1) superfamily that reverses age-related cardiac hypertrophy, improves muscle regeneration and angiogenesis, and maintains progenitor cells in injured tissue. Recently, targeted myocardial delivery of the GDF11 gene in aged mice was found to reduce heart failure and enhance the proliferation of cardiac progenitor cells after myocardial ischemia-reperfusion (I-R). No investigations have as yet explored the cardioprotective effect of exogenous recombinant GDF11 in acute I-R injury, despite the convenience of its clinical application. We sought to determine whether exogenous recombinant GDF11 protects against acute myocardial I-R injury and investigate the underlying mechanism in Sprague-Dawley rats. We found that GDF11 reduced arrhythmia severity and successfully attenuated myocardial infarction; GDF11 also increased cardiac function after I-R, enhanced HO-1 expression and decreased oxidative damage. GDF11 activated the canonical TGF-ß signaling pathway and inactivated the non-canonical pathways, ERK and JNK signaling pathways. Moreover, administration of GDF11 prior to reperfusion protected the heart from reperfusion damage. Notably, pretreatment with the activin-binding protein, follistatin (FST), inhibited the cardioprotective effects of GDF11 by blocking its activation of Smad2/3 signaling and its inactivation of detrimental TGF-ß signaling. Our data suggest that exogenous GDF11 has cardioprotective effects and may have morphologic and functional recovery in the early stage of myocardial I-R injury. GDF11 may be an innovative therapeutic approach for reducing myocardial I-R injury.

Solanum nigrum Linn. water extract inhibits metastasis in mouse melanoma cells in vitro and in vivo.

Metastatic melanoma is an aggressive skin cancer notoriously resistant to current cancer therapies. Thus, new treatment strategies are urgently needed. Solanum nigrum Linn., commonly used in Oriental medicine, has showed antineoplastic activity in human cancer cell lines. The aim of this study was to evaluate the inhibitive effect of S. nigrum Linn. water extract (SNWE) on melanoma metastasis and dissect the underlying mechanisms of SNWE actions. B16-F1 cells were analyzed for migrating and invasive abilities with SNWE treatment, and several putative targets involved in metastatic melanoma were examined. In parallel, primary mouse xenograft and lung metastasis of melanoma models were established to examine the therapeutic potential of SNWE. The results indicated SNWE significantly inhibited B16-F1 cell migration and invasion. Meanwhile, decreased Akt activity and PKCα, Ras, and NF-κB protein expressions were detected in dose-dependent manners. In line with this notion, >50% reduced tumor weight and lung metastatic nodules were observed in 1% SNWE fed mice. This was associated with reduced serum MMP-9 as well as Akt activity and PKCα, Ras, and NF-κB protein expressions. Thus, this work indicates SNWE has potential application for treating metastatic melanoma.

Solanum nigrum L. extract inhibits 2-acetylaminofluorene-induced hepatocarcinogenesis through overexpression of glutathione S-transferase and antioxidant enzymes.

Solanum nigrum L. (SN) is a widespread plant and is regarded as a common relish in the east and the south of Taiwan. Our previous study has found that SN water extract (SNWE) alleviated carbon tetrachloride-induced liver damage in rats. However, the effects of SNWE on chemical-induced hepatic injury and hepatocarcinogenesis remain unclear. Therefore, this study aims to investigate the effects of SNWE on hepatic injury and hepatocarcinogenesis by using 2-acetylaminofluorene (AAF) and AAF/NaNO(2) treatment. The serum biomarkers for hepatic injury, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl transferase, and for hepatocarcinogenesis, alpha-fetoprotein, were determined. Our results showed that AAF treatment led to a significant decrease of body weight and an increase of liver/body weight and serum biomarkers for hepatic injury and hepatocarcinogenesis. Interestingly, the SNWE supplement significantly lowered the liver/body weight and the biomarkers but did not affect the body weight. Further investigation revealed that a SNWE supplement increased the expression of glutathione S-transferase-alpha and -mu, the level of transcription factor for protection from oxidative stress, Nrf2, and the level of downstream targets regulated by Nrf2, including glutathione peroxidase, superoxide dismutase-1, and catalase. Moreover, the effects of SNWE on AAF/NaNO(2)-induced hepatoma were also investigated, and the findings revealed that SNWE suppressed the progression of the hepatoma and resulted in a great increase of the survival rate. Our findings indicate that the SNWE supplement significantly alleviated the AAF-induced hepatic injury and early hepatocarcinogenesis as well as the AAF/NaNO(2)-induced lethal hepatoma, which may result from the overexpression of glutathione S-transferases, Nrf2, and antioxidant enzymes.