Lipid metabolic reprogramming by traditional Chinese medicine and its role in effective cancer therapy.

Epidemiological data have shown a positive correlation between lipid levels and tumor occurrence, such as the correlation between tumor frequency and aggressiveness, and cardiovascular disease, obesity, type 2 diabetes mellitus, and hyperinsulinemia. Therefore, reducing fat accumulation or weakening lipid metabolism may affect the carcinogenic processes of cells. Many studies have shown that traditional Chinese Medicine (TCM) has obvious advantages over traditional therapies in terms of fewer side effects, lower toxicity, and lower economic burden. This paper reviews the mechanism by which TCM regulates lipid metabolism and its antitumor effect through this regulation, with the aim of elucidating the bioactive compounds in TCM with good efficacy and few side effects that can provide promising therapeutic drugs for targeting lipid metabolism reprogramming in cancer.

Changes in Copper, Zinc, Arsenic, Mercury, and Lead Concentrations in Rat Biofluids and Tissues Induced by the "Renqing Changjue" Pill, a Traditional Tibetan Medicine.

The "Renqing Changjue" pill (RQCJ), as an effective prescription of Traditional Tibetan Medicine (TTM), has been widely used in treating advanced gastroenteropathy diseases for over a thousand years. However, the toxicity and adverse effects of TTM have attracted increasing attention because heavy metals may be added as active ingredients. In this work, we introduced a robust model based on endogenous metabolism enabling the study of changes in copper (Cu), zinc (Zn), arsenic (As), mercury (Hg), and lead (Pb) concentrations and the mechanism between biofluids (blood and urine) and tissue (liver, kidney, spleen) samples from rats treated with RQCJ, along with metabolic changes after different treatment time points. Inductively coupled plasma-mass spectrometry was used to monitor the heavy metals. Slightly different trends of heavy metals were observed in rat metabolites. The levels of Hg, As, and Pb were clearly dose-dependent in the tissue and biofluid samples. Basic recovery of Hg and Pb was found after stopping treatment with RQCJ. The accumulation of As was more obvious in the blood, liver, kidney, and spleen; however, Hg was deposited in the kidney. Pb accumulated the most in the spleen. The concentrations of Cu and Zn were constant or accumulated to a certain extent, which could cause the body to have Cu and Zn metabolism disorders in the administration period. Our findings highlight how metal changes and effects on the mechanisms might contribute to the progression of understanding of the toxicity information for RQCJ. Therefore, precautions should be taken in the clinic to monitor the potential toxicity of RQCJ with long-term administration.

Toxicological Risks of Renqingchangjue in Rats Evaluated by 1H NMR-Based Serum and Urine Metabolomics Analysis.

Renqingchangjue (RQCJ), a kind of Traditional Tibetan Medicine, has been widely utilized to treat various gastroenteritis diseases. However, the biosafety and toxicity of RQCJ was still indefinite because of toxic components in RQCJ, which included a variety of heavy metals. Thus, this study was aimed to evaluate the toxicity and expound the toxicological mechanism of RQCJ. In this study, rats were intragastrically administered with different doses of RQCJ for 15 days, and then, the restorative observation period lasted for 15 days. Liver and kidney tissues were collected for histopathological examination, and simultaneously serum and urine samples were collected for 1H nuclear magnetic resonance (1H NMR) spectroscopy analysis and biochemical analysis combined with inductively coupled plasma mass spectrometry (ICP-MS) measurement. The 1H NMR-based metabolomics analysis revealed that the administration of RQCJ significantly altered the concentrations of 14 serum metabolites and 14 urine metabolites, which implied disturbances in energy metabolism, amino acid metabolism, intestinal flora environment, and membrane damage. Besides, the biochemical analysis of serum samples was consistent with the histopathological results, which indicated slight hepatotoxicity and nephrotoxicity. The quantification of As and Hg in urine and serum samples by ICP-MS provided more evidence about the toxicity of RQCJ. This work provided an effective method to systematically and dynamically evaluate the toxicity of RQCJ and suggested that precautions should be taken in the clinic to monitor the potential toxicity of RQCJ.

Tissue metabolomics study to reveal the toxicity of a traditional Tibetan medicine 'Renqing Changjue' in rats.

Renqing Changjue (RQCJ), a precious Traditional Tibetan Medicine (TTM), has been widely used in the management of diseases of the digestive system, toxinosis and pyreticosis. However, in the formula, a significant level of heavy metals, which are potential toxic elements, are present. Therefore, it is important to assess the toxicity of RQCJ dynamically and holistically. In the present study, a 1H NMR metabolomics approach and inductively coupled plasma mass spectrometry (ICP-MS) were implemented to analyze the samples of liver, kidney and spleen from rats treated with RQCJ. The results revealed that 9 metabolites in the liver, 13 metabolites in the kidney and 16 metabolites in the spleen were significantly altered, which suggest that disturbances in TCA cycle, amino acid metabolism, energy metabolism and oxidative stress are produced by successive administration of RQCJ over 15 days. Complemented by histopathology and biochemical assay, the trends of the metabolite levels indicate that RQCJ caused tissue injury to a certain extent, which was evidenced by the high levels of As and Hg in the tissue. The toxic effects of RQCJ were alleviated in liver and kidney during the recovery period, and RQCJ may cause long-term damage in spleen. These findings provide a significant experimental proof on the estimated safety and valuable information about the metabolism of RQCJ, which will be valuable in determining the health risks of the drug.

1H NMR-Based Metabolomics Study of the Toxicological Effects in Rats Induced by "Renqing Mangjue" Pill, a Traditional Tibetan Medicine.

"RenqingMangjue" pill (RMP), as an effective prescription of Traditional Tibetan Medicine (TTM), has been widely used in treating digestive diseases and ulcerative colitis for over a thousand years. In certain classical Tibetan Medicine, heavy metal may add as an active ingredient, but it may cause contamination unintentionally in some cases. Therefore, the toxicity and adverse effects of TTM became to draw public attention. In this study, 48 male Wistar rats were orally administrated with different dosages of RMP once a day for 15 consecutive days, then half of the rats were euthanized on the 15th day and the remaining were euthanized on the 30th day. Plasma, kidney and liver samples were acquired to 1H NMR metabolomics analysis. Histopathology and ICP-MS were applied to support the metabolomics findings. The metabolic signature of plasma from RMP-administrated rats exhibited increasing levels of glucose, betaine, and creatine, together with decreasing levels of lipids, 3-hydroxybutate, pyruvate, citrate, valine, leucine, isoleucine, glutamate, and glutamine. The metabolomics analysis results of liver showed that after RMP administration, the concentrations of valine, leucine, proline, tyrosine, and tryptophan elevated, while glucose, sarcosine and 3-hydroxybutyrate decreased. The levels of metabolites in kidney, such as, leucine, valine, isoleucine and tyrosine, were increased, while taurine, glutamate, and glutamine decreased. The study provides several potential biomarkers for the toxicity mechanism research of RMP and shows that RMP may cause injury in kidney and liver and disturbance of several pathways, such as energy metabolism, oxidative stress, glucose and amino acids metabolism.

Traditional, complementary, and alternative medicine: Focusing on research into traditional Tibetan medicine in China.

As a form of traditional, complementary, and alternative medicine (TCAM), traditional Tibetan medicine has developed into a mainstay of medical care in Tibet and has spread from there to China and then to the rest of the world. Thus far, research on traditional Tibetan medicine has focused on the study of the plant and animal sources of traditional medicines, study of the histology of those plants and animals, chemical analysis of traditional medicines, pharmacological study of those medicines, and evaluation of the clinical efficacy of those medicines. A number of papers on traditional Tibetan medicines have been published, providing some evidence of the efficacy of traditional Tibetan medicine. However, many traditional Tibetan medicines have unknown active ingredients, hampering the establishment of drug quality standards, the development of new medicines, commercial production of medicines, and market availability of those medicines. Traditional Tibetan medicine must take several steps to modernize and spread to the rest of the world: the pharmacodynamics of traditional Tibetan medicines need to be determined, the clinical efficacy of those medicines needs to be verified, criteria to evaluate the efficacy of those medicines need to be established in order to guide their clinical use, and efficacious medicines need to be acknowledged by the pharmaceutical market. The components of traditional Tibetan medicine should be studied, traditional Tibetan medicines should be screened for their active ingredients, and techniques should be devised to prepare and manufacture those medicines.

Alantolactone exhibited anti-herpes simplex virus 1 (HSV-1) action in vitro.

The aim of this study was to determine the inhibitory action of alantolactone, a gradient of traditional Chinese medicine Inulae Radix (Tu-Mu-Xiang), on herpes simplex virus 1 (HSV-1). African green monkey kidney cells (Vero cells) were infected with HSV-1 and the protective effects of alantolactone on Vero cells were examined. At concentrations of 10(-6), 10(-7), and 10(-8) g/mL, alantolactone did not have a marked harmful effect on the viability of Vero cells according to an MTT assay. Based on the cytopathic effect (CPE) and MTT assays, alantolactone at these concentrations exhibited antiviral action and protected cells from being damaged by HSV-1. Results indicated that alantolactone had potent anti-HSV-1 action and provided evidence for use of Inulae Radix in the treatment of HSV-1 infection.

[Chemical constituents of Tibetan medicine kandrakari (I)].

In order to illuminate the effective compounds in Tibetan medicine kandrakari, chemical composition of dry stems of Rubus amabilis were studied by means of various chromatographic techniques, leading to the isolation of 11 compounds. On the basis of spectroscopic data, their structures were elucidated as 1,8-dihydroxy-3,7-dimethoxyxanthone (1), 1-hydroxy-3,7,8-trimethoxyxanthone (2), 1,8-dihydroxy-3,5-dim ethoxyxanthone (3), kaempfero-3-O-(6"-trans-p-coumaroyl) -beta-D-glucopyranoside (4), quercetin (5), kaempferol (6), hyperoside (7), luteolin-7-O-beta-D-glucopy ranoside (8), apigenin-7-O-beta-D-glucopyranoside (9), isovitexin-7-O-glucoside (10), and procyanidin B4 (11). Compounds 1-3 were isolated from the Rubus genus for the first time,and compounds 1-6, 10-11 were isolated from R. amabilis for the first time.