Nourishing Yin traditional Chinese medicine: potential role in the prevention and treatment of type 2 diabetes.

Type 2 diabetes mellitus (T2DM), a common and frequently occurring disease in contemporary society, has become a global health threat. However, current mainstream methods of prevention and treatment, mainly including oral hypoglycemic drugs and insulin injections, do not fundamentally block the progression of T2DM. Therefore, it is imperative to find new ways to prevent and treat diabetes. Traditional Chinese medicine is characterized by multiple components, pathways, and targets with mild and long-lasting effects. Pharmacological studies have shown that nourishing yin traditional Chinese medicine (NYTCM) can play a positive role in the treatment of T2DM by regulating pathways such as the phosphatidylinositol 3-kinase/serine-threonine kinase, mitogen-activated protein kinase, nuclear factor-kappa B, and other pathways to stimulate insulin secretion, protect and repair pancreatic ß cells, alleviate insulin resistance, ameliorate disordered glucose and lipid metabolism, mitigate oxidative stress, inhibit inflammatory responses, and regulate the intestinal flora. The pharmacologic activity, mechanisms, safety, and toxicity of NYTCM in the treatment of T2DM are also reviewed in this manuscript.

Exploring metabolic responses and pathway changes in CHO-K1 cells under varied aeration conditions and copper supplementations using 1 H NMR-based metabolomics.

The optimization of bioprocess for CHO cell culture involves careful consideration of factors such as nutrient consumption, metabolic byproduct accumulation, cell growth, and monoclonal antibody (mAb) production. Valuable insights can be obtained by understanding cellular physiology to ensure robust and efficient bioprocess. This study aims to improve our understanding of the CHO-K1 cell metabolism using 1 H NMR-based metabolomics. Initially, the variations in culture performance and metabolic profiles under varied aeration conditions and copper supplementations were thoroughly examined. Furthermore, a comprehensive metabolic pathway analysis was performed to assess the impact of these conditions on the implicated pathways. The results revealed substantial alterations in the pyruvate metabolism, histidine metabolism, as well as phenylalanine, tyrosine and tryptophan biosynthesis, which were especially evident in cultures subjected to copper deficiency conditions. Conclusively, significant metabolites governing cell growth and mAb titer were identified through orthogonal partial least square-discriminant analysis (OPLS-DA). Metabolites, including glycerol, alanine, formate, glutamate, phenylalanine, and valine, exhibited strong associations with distinct cell growth phases. Additionally, glycerol, acetate, lactate, formate, glycine, histidine, and aspartate emerged as metabolites influencing cell productivity. This study demonstrates the potential of employing 1 H NMR-based metabolomics technology in bioprocess research. It provides valuable guidance for feed medium development, feeding strategy design, bioprocess parameter adjustments, and ultimately the enhancement of cell proliferation and mAb yield.

Health risk assessment for human mercury exposure from Cinnabaris-containing Baizi Yangxin Pills in healthy volunteers Po administration.

BACKGROUND: Cinnabaris (α-HgS), a mineral traditional Chinese material medica, has been used in combination with other herbs manifesting some definite therapeutic effects for thousands of years. But the currently reported mercury poisoning incidents raised the doubts about the safety of Cinnabaris-containing traditional Chinese medicines (TCMs). Baizi Yangxin Pills (BZYXP) is a Cinnabaris-containing TCM widely used in clinical practice. This study evaluated the health risk of mercury exposure from BZYXP in healthy volunteers based on the total mercury and mercury species analysis of blood and urine after single and multiple doses of BZYXP. METHODS: Blood pharmacokinetics and urinary excretion studies of mercury were compared between single (9 g, once daily) and multiple doses (9 g, twice daily, continued for 7 days) of BZYXP. The whole blood and urine samples were collected at the specific points or periods after the administration of BZYXP. The total mercury and mercury species in blood and urine samples were determined by cold vapor-atomic fluorescence spectrometry (CV-AFS) and HPLC-CV-AFS, respectively. RESULTS: The mercury was excreted slowly and accumulated obviously after continuous exposure of BZYXP. Moreover, the well-known neurotoxin methylmercury (MeHg) was detected in blood samples after 7 days' administration of BZYXP. In the urine samples, only Hg(II) was detected. Therefore, long-term use of BZYXP will cause mercury poisoning due to mercury's high accumulative properties and MeHg formation. CONCLUSION: Cinnabaris-containing TCMs such as BZYXP should be restricted to cases in which alternatives are available, and the blood mercury species profile should be monitored during the long-term clinical medication.

Uptake and translocation of organic pollutants in Camellia sinensis (L.): a review.

Camellia sinensis (L.) is a perennial evergreen woody plant with the potential for environmental pollution due to its unique growth environment and extended growth cycle. Pollution sources and pathways for tea plants encompass various factors, including atmospheric deposition, agricultural inputs of chemical fertilizers and pesticide, uptake from soil, and sewage irrigation. During the cultivation phase, Camellia sinensis (L.) can absorb organic pollutants through its roots and leaves. This review provides an overview of the uptake and translocation mechanisms involving the absorption of polycyclic aromatic hydrocarbons (PAHs), pesticides, anthraquinone (AQ), perchlorate, and other organic pollutants by tea plant roots. Additionally, we summarize how fresh tea leaves can be impacted by spraying pesticide and atmospheric sedimentation. In conclusion, this review highlights current research progress in understanding the pollution risks associated with Camellia sinensis (L.) and its products, emphasizing the need for further investigation and providing insights into potential future directions for research in this field.

Natural deep eutectic ready to use extract of astilbin: Super high in vitro bioaccessibility, α-amylase and α-glucosidase enzyme inhibition kinetics.

Astilbin, a natural flavonoid, possesses multiple functionalities, while the poor bioavailability seriously restricts its application in functional food and medicine. Therefore, in this study, a natural deep eutectic solvent (NaDES) with choline chloride: lactic acid (CHCL-LAC) is selected to deliver astilbin by evaluating the bioaccessibility and antioxidant capacity during in vitro gastrointestinal digestion, and the inhibitory effect with underlying mechanism of astilbin-CHCL-LAC against α-amylase/α-glucosidase were investigated. The CHCL-LAC showed significant high astilbin bioaccessibility (84.1% bioaccessible) and DPPH and ORAC antioxidant capacity with 75.7% and 57.7% respectively after 3 h in vitro digestion, which may be attributed by hydrogen bond based supramolecule formed between astilbin and CHCL-LAC. Moreover, significant inhibitions of astilbin-CHCL-LAC on α-amylase (IC50 of 0.67 g/L) and α-glucosidase (IC50 of 0.64 g/L) were observed in mixed competitive and non-competitive manners. The dominant binding force between enzymes and astilbin were the hydrogen and hydrophobic interaction. This is the first time that the underlying mechanisms for astilbin delivered by NaDESs were revealed, suggesting that CHCL-LAC-based NaDESs are promising ready-to-use vehicles of natural inhibitors for carbohydrate-hydrolyzing enzymes.

Influence of biotin intervention on glycemic control and lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Background: Biotin is a water-soluble vitamin acting as a covalently bound coenzyme in regulating energy production. Previous studies have reported that biotin supplementation may influence blood glucose and lipid level in patients with type 2 diabetes mellitus (T2DM). Methods: We searched Pubmed, Embase, and Cochrane library databases up to 8th August 2022 for studies examining the effects of biotin supplementation in T2DM patients. Pooled effects were measured by weighted mean differences (WMDs) with 95% confidence intervals (CI) using random effects models. Inter-study heterogeneity was assessed and quantified. Results: A total of five random controlled trials (RCT), involving 445 participants were included. It was suggested that biotin supplementation for 28 to 90 days significantly decreased the level of fasting blood glucose (FBG) (MD: -1.21 mmol/L, 95% CI: -2.73 to 0.31), total cholesterol (TC) (MD: -0.22 mmol/L, 95% CI: -0.25 to -0.19) and triglycerides (TG) (MD: -0.59 mmol/L, 95% CI: -1.21 to 0.03). No significant beneficial effects were observed on insulin (MD: 1.88 pmol/L 95% CI: -13.44 to 17.21). Evidence for the impact of biotin supplementation on the levels of glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and very low-density lipoprotein cholesterol (VLDL-C) was limited to draw conclusion. Conclusions: Biotin supplementation may decrease FBG, TC and TG levels. However, its influence on insulin is not significant and further studies on the effects of biotin on HbA1c, LDL-C, HDL-C and VLDL-C are expected.

Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome.

In recent years, many natural foods and herbs rich in phytochemicals have been proposed as health supplements for patients with metabolic syndrome (MetS). Theaflavins (TFs) are a polyphenol hydroxyl substance with the structure of diphenol ketone, and they have the potential to prevent and treat a wide range of MetS. However, the stability and bioavailability of TFs are poor. TFs have the marvelous ability to alleviate MetS through antiobesity and lipid-lowering (AMPK-FoxO3A-MnSOD, PPAR, AMPK, PI3K/Akt), hypoglycemic (IRS-1/Akt/GLUT4, Ca2+/CaMKK2-AMPK, SGLT1), and uric-acid-lowering (XO, GLUT9, OAT) effects, and the modulation of the gut microbiota (increasing beneficial gut microbiota such as Akkermansia and Prevotella). This paper summarizes and updates the bioavailability of TFs, and the available signaling pathways and molecular evidence on the functionalities of TFs against metabolic abnormalities in vitro and in vivo, representing a promising opportunity to prevent MetS in the future with the utilization of TFs.

Dissipation pattern and conversion of pyrrolizidine alkaloids (PAs) and pyrrolizidine alkaloid N-oxides (PANOs) during tea manufacturing and brewing.

Pyrrolizidine alkaloids (PAs) and pyrrolizidine alkaloid N-oxides (PANOs) are toxic secondary metabolites in plants, and one kind of main exogenous pollutants of tea. Herein, the dissipation pattern and conversion behavior of PAs/PANOs were investigated during tea manufacturing and brewing using ultra high-performance liquid chromatography tandem mass spectrometry. Compared with PAs (processing factor (PF) = 0.73-1.15), PANOs had higher degradation rates (PF = 0.21-0.56) during tea manufacturing, and drying played the most important role in PANOs degradation. Moreover, PANOs were firstly discovered to be converted to corresponding PAs especially in the time-consuming (spreading of green tea manufacturing and withering of black tea manufacturing) and high-temperature tea processing (drying). Moreover, higher transfer rates of PANOs (≥75.84%) than that of PAs (≤56.53%) were observed during tea brewing. Due to higher toxicity of PAs than PANOs, these results are conducive to risk assessment and pollution control of PAs/PANOs in tea.

Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is the main regulator of physiological angiogenesis during embryonic development, bone growth, and reproductive function, and it also participates in a series of pathological changes. Traditional Chinese medicine (TCM), with a history of more than 2000 years, has been widely used in clinical practice, while the exploration of its mechanisms has only begun. This review summarizes the research of recent years on the influence of TCM on VEGF. It is found that many Chinese medicines and recipes have a regulatory effect on VEGF, indicating that Chinese medicine has broad prospects as a complementary and alternative therapy, providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.

Boosted growth performance, immunity, antioxidant capacity and disease resistance of crucian carp (Carassius auratus) by single or in combination dietary Bacillus subtilis and xylo-oligosaccharides.

In this study, a total of 420 healthy crucian carp (9.77 ± 0.04 g) were randomly divided into CK, B·S, XOS and B·S + XOS group, and cultured for 8 weeks. Results showed that the dietary Bacillus subtilis (B. subtilis) and xylo-oligosaccharides (XOS) can significantly increased the final weight, weight gain, specific growth rate, feed efficiency, protein efficiency and survival rate of crucian carp. Dietary B. subtilis and XOS can significantly increased the activities of catalase, glutathione, superoxide dismutase and total antioxidant capacity, significantly decreased the contents of malondialdehyde, and significantly increased the activities of alkaline phosphatase, acid phosphatase, lysozyme and the contents of complement component 3,4 and immunoglobulin M in crucian carp serum. In addition, compared with CK group, the expression levels of TGF-ß and IL-10 in B·S, XOS and B·S + XOS group were significantly increased, and the expression levels of TNF-α, HSP90, IL-1ß, TLR4 and MyD88 were significantly decreased. Supplementation of B. subtilis and XOS can also improve the intestinal tissue morphology of crucian carp. After injection of 1 × 107 CFU/mL Aeromonas hydrophila (A. hydrophila), compared with CK group, the survival rates of the B·S group, the XOS group and the B·S + XOS group were increased by 13.98%, 10.56% and 30.74%, respectively. These results show that dietary B. subtilis and XOS can significantly improve the growth performance, antioxidant capacity, immunity and resistance to A. hydrophila of crucian carp, and the combined effect is better than that of single addition.

A comprehensive update: gastrointestinal microflora, gastric cancer and gastric premalignant condition, and intervention by traditional Chinese medicine.

With the recent upsurge of studies in the field of microbiology, we have learned more about the complexity of the gastrointestinal microecosystem. More than 30 genera and 1000 species of gastrointestinal microflora have been found. The structure of the normal microflora is relatively stable, and is in an interdependent and restricted dynamic equilibrium with the body. In recent years, studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer (GC) and precancerous lesions. So, restoring the balance of gastrointestinal microflora is of great significance. Moreover, intervention in gastric premalignant condition (GPC), also known as precancerous lesion of gastric cancer (PLGC), has been the focus of current clinical studies. The holistic view of traditional Chinese medicine (TCM) is consistent with the microecology concept, and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract, restoring the homeostasis of gastrointestinal microflora to prevent canceration. However, large gaps in knowledge remain to be addressed. This review aims to provide new ideas and a reference for clinical practice.

Selenium-enriched Bacillus subtilis reduces the effects of mercury-induced on inflammation and intestinal microbes in carp (Cyprinus carpio var. specularis).

Mercury (Hg) is a global pollutant that affects the health of humans and ecosystems. Selenium (Se) is an essential trace element for many organisms including humans. Bacillus subtilis is one of the main probiotics used in aquaculture, and has a certain adsorption effect on heavy metals. The interaction between Hg and Se was rigorously studied, especially due to the observation of the protective effect of Se on Hg toxicity. The objective of this study was to research the effects of Hg, Se, and B. subtilis on inflammation and intestinal microbes in common carp. The common carp was exposed to Hg (0.03 mg/L), and 105 cfu/g Se-rich B. subtilis was added to the feed. After 30 days of feeding, samples were taken to evaluate the growth performance, serological response, inflammatory response, and intestinal microbial changes. In this study, when fish were exposed to Hg, the growth performance of the Se-rich B. subtilis plus 0.03 mg/L Hg fish group was lower than that of the control group and higher than 0.03 mg/L Hg; The levels of serum immunoglobulin M (IgM) and lysozyme (LZM) decreased, but after supplementation with Se-rich B. subtilis, the levels of LZM and IgM increased; Hg treatment significantly upregulated the mRNA expression of interleukin-1ß (IL-1ß), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and nuclear factor-kB (NF-κB P65), but downregulated the mRNA expression of interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß) and NF-kappa-B inhibitor alpha (IkBα). However, compared with the Hg group, the Se-rich B. subtilis plus Hg group can significantly increase the mRNA expression levels of IL-1ß, IL-8, TNF-α, and NF-κB P65, but reduce the regulation of IL-10, TGF-ß, and IkBα expression. Through the analysis of the microbiological, we found that the Hg group was mainly composed of Aeromonas sobria and Aeromonas hydrophila. However, in the Se-rich B. subtilis treatment group, we found that Aeromonas sobria was significantly less than the Hg group. Se-rich B. subtilis improves Hg-induced intestinal microbial changes, alleviates the abundance of Aeromonas, and alleviates the inflammation of the fish. The results of this study show that Se-rich B. subtilis dietary supplements can effectively protect common carp against Hg toxicity.

Evaluation of the effects of Astragalus polysaccharides as immunostimulants on the immune response of crucian carp and against SVCV in vitro and in vivo.

This experiment was conducted to evaluate the immunomodulatory effect and antiviral activity of Astragalus polysaccharides (APS) in crucian carp and epithelioma papulosum cyprinid (EPC) cells. Two diets containing 0 and 2 g/kg, APS were fed crucian carp for 56 days. The results showed that supplementation with APS significantly upregulated the immune-related indices including the levels of IgM, the activities of LZM, AKP and ACP, and the contents of C3 and C4. At the same time, compared with the CK group, adding APS to the feed significantly upregulated the expression of IL-8, IL-10, IL-1ß, IFN-α, IFN-γ, MyD88, TGF-ß and TNF-α in the spleen, kidney, liver and intestine of crucian carp. In addition, when the crucian carp were injected with SVCV, the survival rates of fish in the APS group and the control group were 48.87% and 13.76%, respectively. These results indicated that dietary APS could improve the resistance of crucian carp against SVCV infection. APS also significantly decreased viral titer and inhibited apoptosis induced by SVCV in EPC cells. These results indicated that APS could stimulate the immune response of crucian carp and improve the abilities of crucian carp and EPC cells to resist SVCV infection.

Two NPF transporters mediate iron long-distance transport and homeostasis in Arabidopsis.

Iron (Fe) transport and reallocation are essential to Fe homeostasis in plants, but it is unclear how Fe homeostasis is regulated, especially under stress. Here we report that NPF5.9 and its close homolog NPF5.8 redundantly regulate Fe transport and reallocation in Arabidopsis. NPF5.9 is highly upregulated in response to Fe deficiency. NPF5.9 expresses preferentially in vasculature tissues and localizes to the trans-Golgi network, and NPF5.8 showed a similar expression pattern. Long-distance Fe transport and allocation into aerial parts was significantly increased in NPF5.9-overexpressing lines. In the double mutant npf5.8 npf5.9, Fe loading in aerial parts and plant growth were decreased, which were partially rescued by Fe supplementation. Further analysis showed that expression of PYE, the negative regulator for Fe homeostasis, and its downstream target NAS4 were significantly altered in the double mutant. NPF5.9 and NPF5.8 were shown to also mediate nitrate uptake and transport, although nitrate and Fe application did not reciprocally affect each other. Our findings uncovered the novel function of NPF5.9 and NPF5.8 in long-distance Fe transport and homeostasis, and further indicated that they possibly mediate nitrate transport and Fe homeostasis independently in Arabidopsis.

[Research progress in establishment of N-methyl-N'-nitro-N-nitroso-guanidine-induced rat model of Precancerous lesion of gastric cancer].

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.

Effect of selenium-rich Bacillus subtilis against mercury-induced intestinal damage repair and oxidative stress in common carp.

Mercury (Hg) poisoning in humans and fish represents a significant global problem. Hg is one of the most dangerous threats to the aquatic ecosystem due to its high toxicity. Mercury has a high oxidative stress-inducing potential, and can compounds exert toxic effects by interacting with many important enzymes involved in the regulation of antioxidants. Selenium (Se) supplementation can reactivate the mercury-inhibited enzymes viability. The probiotic Bacillus subtilis is widely used in aquaculture, and it has a certain adsorption effect on heavy metals. The interactions between Hg and Se have been rigorously investigated, particularly due to the observed protective effects of Se against Hg toxicity. The objective of this study was to evaluate whether Se-rich B. subtilis ameliorated Hg-induced toxicity in C. carpio var. specularis. Fish were exposed to waterborne Hg (0.03 mg/L) and fed a diet supplemented with 105 cfu/g Se-rich B. subtilis for 30 days. Fish were sampled, antioxidant activity, and Intestinal damage repair were assessed. Our results indicated that Se-rich B. subtilis protected the Intestinal from Hg-induced morphological changes. Hg treatment significantly decreased the activity levels of SOD, CAT and GSH-PX while increasing the activity levels of MDA, GST, and GSH. Hg treatment also upregulated the mRNA expression of Nrf2, CAT, GSH-PX and HO-1, and reduced expression of keap1. Se-rich B. subtilis had a significant protective effect against Hg-induced oxidative stress.

Based on Systematic Pharmacology: Molecular Mechanism of Siwei Jianbu Decoction in Preventing Oxaliplatin-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect caused by chemotherapy drugs, and its existence seriously affects the quality of life of patients. We first established an oxaliplatin-induced peripheral neuropathy (OIPN) model and then measured and evaluated mechanical hyperalgesia, thermal nociception, cold allodynia, and intraepidermal nerve fiber (IENF) density to determine Siwei Jianbu Decoction's role in preventing OIPN. Then, we conducted a systematic pharmacological study that revealed important roles for the MAPK signaling pathway and proinflammatory immune pathway and confirmed these roles by western blot, immunofluorescence, and qPCR. The data show that Siwei Jianbu Decoction can effectively prevent oxaliplatin-induced neuroinflammation by inhibiting an increase in NF-κB expression via downregulation of p-ERK1/2 and p-p38. The present study showed that SWJB may be beneficial in preventing oxaliplatin-induced peripheral neuropathy.

Siwei Jianbu decoction improves painful paclitaxel-induced peripheral neuropathy in mouse model by modulating the NF-κB and MAPK signaling pathways.

BACKGROUND: Paclitaxel, a commonly used chemotherapeutic agent, is usually associated with peripheral neuropathy. Paclitaxel induced peripheral neuropathy (PIPN) can be dose limiting and may have detrimental influence on patients' quality of life. However, the mechanism of PIPN remains unclear. Medicinal herbs and their formulas might offer neuronal protection with their multitarget and integrated benefits in chemotherapy-induced peripheral neuropathy (CIPN). Siwei Jianbu decoction (J12) is a classic formula of traditional Chinese medicine which can promote blood circulation and treat diabetic nephropathy in clinical with the symptoms of weakness and pain. METHODS: The effects of J12 were treated in C57BL/6 mice before injected with Paclitaxel.Behaviour studies: Measurement of mechanical hyperalgesia, thermal nociception and cold allodynia. On the last day at the end of week 6, DRGs were obtained from mice for western blot and immunohistochemical analysis containing NF-κB, p-ERK1/2 and p-SAPK/JNK protein expression. Quantitative real-time polymerase chain reaction: mRNA expression of NF-κB, IL-1ß and TNF-α was analyzed. Additionally, the blood samples collected from the eye socket of the mouse were prepared to examine the levels of NF-κB, TNF-α, IL-6 and IL-1ß using ELISA assay kits. RESULTS: Hypersensitivity tests and pathology analysis have demonstrated that J12 could improve paclitaxel-induced peripheral pain. J12 acts by inhibiting the activation of (C-Jun N-terminal kinases) JNK, (extracellular signal-regulated kinase) ERK1/2 phosphorylation in (Mitogen-activated protein kinases) MAPK signaling pathway and the nuclear factor-κB (NF-κB) in C57BL/6 mice model, J12 also inhibits the production of inflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and IL-6. CONCLUSION: The present study showed that J12 ameliorates paclitaxel-induced peripheral neuropathic pain.

Toxicity and risk assessment of mercury exposures from cinnabar and Baizi Yangxin Pills based on pharmacokinetic and tissue distribution studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Baizi Yangxin Pills (BZYXP), a popular cinnabar (α-HgS) contained Traditional Chinese Medicines (TCMs) is widely used in clinical trials. However, mercury is one of the most toxic elements. The adverse effects of cinnabar-containing TCMs have been occasionally reported in recent years, leading to the growing concerns about their toxicity and safety. AIM OF THE STUDY: The health risks of BZYXP and cinnabar related to the mercury exposures were evaluated through blood pharmacokinetic and tissue distribution studies in rats. MATERIALS AND METHODS: The distribution of absorbed mercury in rats' blood and tissues were measured by the developed cold-vapor atomic fluorescence spectrometric method. And the tissue damages were determined through the histopathological examinations. For single dose study, the low and high oral doses were equivalent to 1 and 10-fold therapeutic dose, respectively. The multiple doses study was conducted at low and high dose levels every 12 h for 30 consecutive days. RESULTS: Significant differences of mercury blood pharmacokinetic and tissue distribution characteristics were observed between the corresponding BZYXP and cinnabar groups. The herbal ingredients in BZYXP promoted the absorption of bio-accessible mercury of cinnabar and prolonged the elimination process, posing potential health risks. Although mercury was found easily accumulated in kidney, liver and brain tissues, kidney and liver didn't show obvious damages even after 30 days consecutive administration of BZYXP or cinnabar at 10-fold clinically equivalent doses. But brain did show some histopathological changes, and autonomic activities of rats decreased, pointing the potential neurotoxicity. CONCLUSIONS: Mercury tend to be accumulated especially when over-dose or prolonged medication with cinnabar-containing TCMs are given. The mercury exposures even at therapeutic doses of BZYXP or cinnabar do pose health risks from the neurotoxicity point of view.

[Pharmacokinetics of mercury after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule in rats].

Fufang Niuhuang Xiaoyan capsule was a classical compound prescription with the efficacy of heat-clearing, detoxification, sedation and anti-inflammation, with cinnabaris as one of its active ingredients. The study focuses on the pharmacokinetics of mercury in rats after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule, in order to explore the effect of combined traditional Chinese medicines on mercury metabolism. In this study, the method of nitric-perchloric acid digestion system coupled with cold atomic-atomic fluorescence spectroscopy (CV-AFS) was adopted to accurately determine mercury in whole blood of rats. Fufang Niuhueng Xiaoyan capsule had three dose schemes of oral administration, namely equivalent clinical dose, 3 times of equivalent clinical dose and 10 times of equivalent clinical dose; And the doses of oral administration of cinnabaris was calculated according to that of Fufang Niuhuang Xiaoyan capsule. SPF grade healthy SD rats were fasted overnight before the oral administration with cinnabaris suspension (or Fufang Niuhuang Xiaoyan capsule suspension). After oral administration of different doses of cinnabaris, no obvious changes in tmax and MRT were observed, while Cmax/dose, AUC0-48 h/dose and AUC0-∞/dose decreased with the increase in dose, indicating that total mercury absorption in body was declining. As the dose increased, Ke, CL/F decreased, and t1/2 increased, indicating that the elimination slowed down, and mercury metabolism showed non-linear dynamic characteristics within a certain range of dose (22-220 mg•kg⁻¹). The total mercury metabolism in the whole blood of rats after oral administration with different doses of Fufang Niuhuang Xiaoyan capsule also showed non-linear dynamic characteristics. The results were correlated with the low solubility of cinnabaris in the body. Compared with cinnabaris, Fufang Niuhuang Xiaoyan capsule showed no obvious changes in V/F and MRT, while Ke, CL/F, tmax decreased, and t1/2, Cmax/dose, AUC0-48 h/dose, AUC0-∞/dose increased significantly. The results showed that Fufang Niuhuang Xiaoyan capsule accelerated absorption, slowed down elimination and improved the total absorption of mercury in the whole blood, indicating that Fufang Niuhuang Xiaoyan capsule may contain components for promoting absorption and alleviating elimination of mercury. Fufang Niuhuang Xiaoyan capsule had an impact on the pharmacokinetics of cinnabaris, and long-term administration of cinnabaris (Fufang Niuhuang Xiaoyan capsule) was possible to cause accumulation of mercury in the body. This study could explain changes in efficacy of Fufang Niuhuang Xiaoyan capsule, evaluate the rationality of compound medicines containing toxic elements and provide scientific basis for the rational and safe use of Fufang Niuhuang Xiaoyan capsule.