Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

NMR-based metabolomics approach to evaluate the toxicological risks of Tibetan medicine 'Ershiwuwei Shanhu' pill in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Ershiwuwei Shanhu' Pill (ESP) is a classic Tibetan medicine to treat neurological disorders in nervous system, especially for neurological pains and epilepsy. It contains many Tibet-specific mineral medicines, among which Halloysite (Halloysitum rubrum, HR) was regarded as the main active one. As mineral medicines contain heavy metals with poor solubility, the doubts about its safety restricted its clinical application and further development. AIM OF THE STUDY: A 7-day acute toxicity of ESP and its main active mineral medicine HR was systematically studied for investigating the safety of ESP and exploring the role of HR in ESP's potential toxicity. MATERIALS AND METHODS: In this study, the acute oral toxicity assessment of formula-ESP and HR were performed on rats for 7 days at doses equivalent to 10 (1 g/kg) and 40 times (4 g/kg) the typical clinical dose (0.1 g/kg). 1H NMR based metabolomics profiling, aided with biochemical analysis and histopathology, was conducted to explore the global metabolic changes in the livers and kidneys of the administrated rats. RESULTS: High-dose HR caused oxidative stress, energy metabolism disorders, purine metabolism impairments and amino acid metabolism imbalance in rats, resulting in hepatotoxicity and nephrotoxicity, which in accordance with the increased biochemical index in blood (ALT, AST, BUN and CRE). ESP (low-dose) induced metabolites changes were far more less than HR in livers, showcasing the distinct advantage of formula in reducing toxicity. Furthermore, low-dose ESP disturbed renal metabolism in a way similar to high-dose HR, which implies that HR might be the major source of the potential nephrotoxicity of ESP. CONCLUSION: HR exhibited potential hepatoxicity and nephrotoxicity, but the formula- 'Ershiwuwei Shanhu' Pill which contains HR is considered relatively safe.

Acute hepatotoxicity and nephrotoxicity risk assessment of the Tibetan medicine 25 flavors of the turquoise pill based on 1H-NMR metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics.

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

Evaluation of hepatotoxicity potential of a potent traditional Tibetan medicine Zuotai.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuotai (gTso thal) has a long history in the treatment of cardiovascular disease, liver and bile diseases, spleen and stomach diseases as a precious adjuvant in Tibetan medicine. However, Zuotai is a mercury preparation that contains 54.5% HgS. Its application has always been controversial. AIM OF THE STUDY: To evaluate the toxicological effects of Zuotai in hepatocytes and in zebrafish. MATERIALS AND METHODS: MTT was used to determine the survival rate of hepatocytes; Hoechst and TUNEL staining were used to detect the apoptosis cells; Western blot and RT-qPCR assay were used to determine the expression levels of the protein and mRNA; Liver morphology observation and H&E staining were used to evaluate the hepatotoxicity of Zuotai in Zebfrafish. RESULTS: The survival rate of L-02 cells, HepG2 cells and RBL-2A cells reduced by Zuotai (10-4-0.1 mg/mL) in a dose and time-dependent manner. Zuotai (0.1 mg/mL) induced HepG2 cells shrinkage, condensation and fragmentation and increased the number of apoptosis cells. The protein expression levels of cleaved Caspase-3 and Bax were increased and the expression levels of Bcl-2 were reduced after HepG2 cells exposed to Zuotai (10-4-0.1 mg/mL) for 24 h. In addition, Zuotai (0.2 mg/mL) induced the darker liver color of the larval zebrafish and changed the liver morphologic of adult zebrafish. Zuotai (0.2 mg/mL) also increased the mRNA levels of CYP1A1, CYP1B1 and MT-1 in the liver of adult zebrafish. However, no significantly hepatotoxicity was observed after hepatocytes and zebrafish exposed to HgS at the same dose. CONCLUSIONS: Results showed that Zuotai induced hepatotoxicity effectively under a certain dose but its hepatotoxicity likely occurs via other mechanisms that did not depend on HgS.

Evaluation of the potential nephrotoxicity and mechanism in rats after long-term exposure to the traditional Tibetan medicine tsothel.

CONTEXT: Tsothel, a traditional Tibetan medicine, is regarded as 'the king of essences'. Nevertheless, tsothel has aroused serious concern regarding its biosafety because its main component is HgS. Unfortunately, toxicological studies on tsothel are scarce. OBJECTIVE: As inorganic mercury has high affinity for the kidney, the present investigation was designed to determine the potential nephrotoxicity and mechanism of tsothel. MATERIALS AND METHODS: Sprague-Dawley rats were orally administered different doses of tsothel (0, 66.70, 33.35 and 16.68 mg/kg) daily for 180 days, followed by the withdrawal of tsothel for 120 days. Then, the related nephrotoxicity was examined by the ICP-MS, ELISA, colorimetric, RT-PCR, HE staining, immunohistochemical staining and flow cytometry methods. RESULTS: Although tsothel administration led to a large accumulation of Hg (794.25 ± 464.30 ng/g in the 66.70 mg/kg group, 775.75 ± 307.89 ng/g in the 33.35 mg/kg group and 532.60 ± 356.77 ng/g in the 16.68 mg/kg group) in the kidney after 120 days of tsothel withdrawal, the blood CREA and BUN, urinary Kim-1, NAG, RBP and ß2-MG, renal SOD, MDA, pathology, proliferation, apoptosis and cell cycle had no significant changes compared with the control group. Additionally, the high GSH content (318.87 ± 44.19 nmol/mL in the 33.35 mg/kg group) and the relative expression levels of Kim-1 (1.08 ± 0.11 in the 33.35 mg/kg group), MT-1 (1.46 ± 0.10 in the 66.70 mg/kg group, 1.61 ± 0.19 in the 33.35 mg/kg group and 1.57 ± 0.14 in the 16.68 mg/kg group) and GST-Pi (1.76 ± 0.89 in the 33.35 mg/kg group) mRNA recovered to normal after tsothel withdrawal. Interestingly, the change trend of GST-Pi gene expression was consistent with the change trend of GSH activity. CONCLUSIONS: Overall, our study shows that tsothel administration did not induce overt nephrotoxicity but did have reversible stress-related effects. These results suggest that tsothel affects stress response mechanisms with the involvement of detoxifying enzyme systems. The formulation method and chemotype could play a role in the reduced toxicity potential of tsothel compared to common mercurials.

Is mercury in Tibetan Medicine toxic? Clinical, neurocognitive and biochemical results of an initial cross-sectional study.

Mercury an important therapeutic substance in Tibetan Medicine undergoes complex "detoxification" prior to inclusion in multi-ingredient formulas. In an initial cross-sectional study, patients taking Tibetan Medicine for various conditions were evaluated for mercury toxicity. Two groups were identified: Group 1, patients taking " Tsothel" the most important detoxified mercury preparation and Group 2, patients taking other mercury preparations or mercury free Tibetan Medicine. Atomic fluorescence spectrometry of Tibetan Medicine showed mercury consumption 130 µg/kg/day (Group 1) and 30 µg/kg/day (Group 2) ( P ≤ 0.001), levels above EPA (RfDs) suggested threshold (0.3 µg/kg /day) for oral chronic exposure. Mean duration of Tibetan Medicine treatment was 9 ± 17 months (range 3-116) (Group 1) and 5 ± 1.96 months (range 1-114) (Group 2) (NS) with cumulative days of mercury containing Tibetan Medicine, 764 days ± 1214 (range 135-7330) vs. 103 days ± 111 (range 0-426), respectively ( P ≤ 0.001). Comparison of treatment groups with healthy referents (Group 3) not taking Tibetan Medicine showed no significant differences in prevalence of 23 non-specific symptoms of mercury toxicity, abnormal neurological, cardiovascular and dental findings and no correlation with mercury exposure variables; consumption, cumulative treatment days, blood/ urine Hg. Liver and renal function tests in treatment groups were not significantly increased compared to referents, with mean urine Beta2 Microglobulin within the normal range and not significantly associated with Hg exposure variables after correcting for confounding variables. Neurocognitive testing showed no significant intergroup differences for Wechsler Memory Scale, Grooved Pegboard, Visual Retention, but Group1 scores were better for Mini-Mental, Brief Word Learning, Verbal Fluency after correcting for confounding variables. These results suggest mercury containing Tibetan Medicine does not have appreciable adverse effects and may exert a possible beneficial effect on neurocognitive function. Since evidence of mercury as a toxic heavy metal, however, is well known, further analysis of literature on mercury use in other Asian traditional systems is highly suggested prior to further studies.

Tibetan medicine for cancer: an overview and review of case studies.

INTRODUCTION: Tibetan medicine (TM) is a whole systems medical approach that has had growing interest in the West. However, minimal research, particularly with cancer, has been conducted. The purpose of this article is to provide an overview of TM and describe a clinical case review study to obtain preliminary evidence of TM's safety and effect on patients treated for cancer or hematologic disorders. METHODS: A retrospective case review was conducted in India and cases met the following inclusion criteria: (a) confirmed diagnosis of cancer or hematologic disorder by standard Western biomedical diagnostic tests, (b) either treated exclusively with TM or received insufficient Western treatment followed by TM and (c) were in remission or had stable disease at least 2 years after start of TM. RESULTS: Three cases were identified, 1 solid tumor and 2 hematologic diseases: Case 1--poorly to moderately differentiated adenocarcinoma of the stomach, positive lymph nodes and mucosal infiltration, with clear scans and excellent quality of life 29 months later ; Case 2--chronic myelogenous leukemia with normalization of hematologic labs within 3 months of starting TM and stable 4 years later; and Case 3--red cell aplasia improved significantly and reversed dependence on blood transfusions with TM. None of the cases experienced demonstrable adverse effects from TM. CONCLUSIONS: This limited case review found TM to be safe and have positive effects on quality of life and disease regression and remission in patients with cancer and blood disorders. Further exploration and investigation using rigorous methods is warranted.