Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases.

The Vitamin D receptor (VDR) is a crucial nuclear receptor that plays a vital role in various physiological functions. To a larger extent, the genomic effects of VDR maintain general wellbeing, and its modulation holds implications for multiple diseases. Current evidence regarding using vitamin D or its synthetic analogs to treat non-communicable diseases is insufficient, though observational studies suggest potential benefits. Traditional Chinese medicines (TCMs) and bioactive compounds derived from natural sources have garnered increasing attention. Interestingly, TCM formulae and TCM-derived bioactive compounds have shown promise in modulating VDR activities. This review explores the intriguing potential of TCM and bioactive compounds in modulating VDR activity. We first emphasize the latest information on the genetic expression, function, and structure of VDR, providing a comprehensive understanding of this crucial receptor. Following this, we review several TCM formulae and herbs known to influence VDR alongside the mechanisms underpinning their action. Similarly, we also discuss TCM-based bioactive compounds that target VDR, offering insights into their roles and modes of action.

Genome-scale transcriptomic insights into the gene co-expression network of seed abortion in triploid Siraitia grosvenorii.

BACKGROUND: Siraitia grosvenorii (Swingle) C. Jeffrey, also known as Luohanguo or monk fruit, is a famous traditional Chinese medicine ingredient with important medicinal value and broad development prospects. Diploid S. grosvenorii has too many seeds, which will increase the utilization cost of active ingredients. Thus, studying the molecular mechanism of seed abortion in triploid S. grosvenorii, identifying the abortion-related genes, and regulating their expression will be a new direction to obtain seedless S. grosvenorii. Herein, we examined the submicroscopic structure of triploid S. grosvenorii seeds during abortion. RESULTS: Upon measuring the endogenous hormone content, we found that abscisic acid (ABA) and trans-zeatin (ZR) levels were significantly downregulated after days 15 and 20 of flowering. RNA sequencing of triploid seeds at different developmental stages was performed to identify key genes regulating abortion in triploid S. grosvenorii seeds. Multiple genes with differential expression between adjacent stages were identified; seven genes were differentially expressed across all stages. Weight gene co-expression network analysis revealed that the enhancement of monoterpene and terpene metabolic processes might lead to seed abortion by reducing the substrate flow to ABA and ZR. CONCLUSIONS: These findings provide insights into the gene-regulatory network of seed abortion in triploid S. grosvenorii from different perspectives, thereby facilitating the innovation of the breeding technology of S. grosvenorii.

Traditional Chinese medicine against COVID-19: Role of the gut microbiota.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has become a public health concern worldwide. In addition to respiratory symptoms, some COVID­19 patients also show various gastrointestinal symptoms and even consider gastrointestinal symptoms to be the first manifestation. A large amount of evidence has shown that SARS-CoV-2 infection could disrupt the gut microbiota balance, and disorders of the gut microbiota could aggravate the condition of COVID-19 patients. Therefore, maintaining the gut microbiota balance is expected to become a potential new therapeutic target for treating COVID-19. Traditional Chinese medicine (TCM) has significant effects in all stages of the prevention and treatment of COVID-19. It can adjust the gut microbiota and is an ideal intestinal microecological regulator. This review summarizes the advantages and clinical efficacy of TCM in the treatment of COVID-19 and expounds on the relationship between TCM and the gut microbiota, the relationship between COVID-19 and the gut microbiota, the mechanism of gut microbiota disorders induced by SARS-CoV-2, the relationship between cytokine storms and the gut microbiota, and the role and mechanism of TCM in preventing and treating COVID-19 by regulating the gut microbiota to provide new research ideas for TCM in the prevention and treatment of COVID-19.

Enantioselectivity of indoxacarb during the growing, processing, and brewing of tea: Degradation, metabolites, and toxicities.

Chiral pesticides are unique hazardous materials. Here, we systematically studied the potentially harmful products of enantioselective indoxacarb degradation throughout tea growth, processing, and brewing and tested their toxicity to tea geometrid larvae and honeybees. The half-lives of S-indoxacarb and R-indoxacarb during tea growth were 2.6 d and 3.3 d, respectively. There was a trend toward the production of S-indoxacarb from R-indoxacarb. The degradation products IN-JT333, IN-MK638, IN-MF014, and IN-KG433 were also characterized in tea growth and processing and detected. IN-JT333, previously known as a direct insecticidal compound produced by the enzymatic transformation of indoxacarb in insects, was first found in plant samples. The fixation and rolling of green tea and the rolling of black tea were the most important steps that affected indoxacarb and its degradation products. The leaching rates of R-indoxacarb and S-indoxacarb were slightly higher in green tea than in black tea. The maximum leaching rates of IN-MK638 and IN-MF014 during the brewing process reached 89.9% and 94.1%, respectively. Contact toxicity tests with honeybees and tea geometrid larvae in the lab showed that the relative toxicities of the compounds could be ranked as follows: S-indoxacarb > indoxacarb (3S + 1R) ≫ R-indoxacarb. TEST toxicity predictions showed that relative toxicities were ranked IN-KG433 > indoxacarb > IN-JT333 > IN-MK638 > IN-MF014. The toxicity of the degradation product IN-KG433 is higher than that of indoxacarb itself, and its maximum leaching rate is as high as 88.2%. It therefore transfers readily from processed tea to the tea infusion during the brewing process. These findings indicate the need to pay attention to the risk of metabolites and enantiomeric differences and provide new, comprehensive insight into the risk factors for indoxacarb in tea and are relevant to the study of other chiral pesticides.

Shufeiya Recipe Improves Monocrotaline-Induced Pulmonary Hypertension in Rats by Regulating SIRT3/FOXO3a and Its Downstream Signaling Pathways.

Pulmonary hypertension (PH) is a chronic and progressive disease caused by obstructions and functional changes of small pulmonary arteries. Current treatment options of PH are costly with patients needing long-term taking medicine. The traditional Chinese medicine (TCM) compound "Shufeiya Recipe" was used to intervene in monocrotaline- (MCT-) induced pulmonary hypertension in rats. The rats were randomly divided into the control group, model group, positive drug (Sildenafil) group, and Shufeiya Recipe low-, moderate-, and high-dose groups. The improvement effect of the Shufeiya Recipe on the mean pulmonary artery pressure (mPAP) was assessed in PH rats, and pathological staining was used to observe the pathological changes of lung tissue. The impact of the Shufeiya Recipe on oxidative stress damage in rats with pulmonary hypertension and the regulation of SIRT3/FOXO3a and its downstream signaling pathways were determined. The results showed that Shufeiya Recipe could significantly downregulate mPAP and improve lung histopathological changes; downregulate serum levels of reactive oxygen species (ROS); upregulate the concentrations of COX-1 and COX-2 and the activity of Mn-SOD; inhibit oxidative response damage; promote the protein expression of SIRT3, FOXO3a, p-PI3K, p-AKT, and p-eNOS; increase the level of expression of NO, sGC, cGMP, and PKG; and downregulate the level of protein expression of Ras, p-MEK1/2, p-ERK1/2 and c-fos. These results indicate that Shufeiya Recipe can improve MCT-induced pulmonary hypertension in rats by regulating SIRT3/FOXO3a and its downstream PI3K/AKT/eNOS and Ras/ERK signaling pathways.

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) is an emergent infectious pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and pathogenic. COVID-19 has rapidly swept across the world since it was first discovered in December 2019 and has drawn significant attention worldwide. During the early stages of the outbreak in China, traditional Chinese medicines (TCMs) were involved in the whole treatment process. As an indispensable part of TCM, Chinese patent medicines (CPMs) played an irreplaceable role in the prevention and treatment of this epidemic. Their use has achieved remarkable therapeutic efficacy during the period of medical observation and clinical treatment of mild, moderate, severe, and critical cases and during convalescence. In order to better propagate and make full use of the benefits of TCM in the treatment of COVID-19, this review will summarize the potential target of SARS-CoV-2 as well as the theoretical basis and clinical efficacy of recommended 22 CPMs by the National Health Commission and the Administration of TCM and local provinces or cities in the treatment of COVID-19. Additionally, the study will further analyze the drug composition, potential active ingredients, potential targets, regulated signaling pathways, and possible mechanisms for COVID-19 through anti-inflammatory and immunoregulation, antiviral, improve lung injury, antipyretic and organ protection to provide meaningful information about the clinical application of CPMs.

Danlou Fang reduces microvascular obstruction through the endothelial/inducible nitric oxide synthase pathway in a rat model.

OBJECTIVE: To investigate the efficacy of the Danlou Fang (DL) Traditional Chinese Medicine formula on microvascular obstruction (no-reflow) through the endothelial/inducible nitric oxide synthase (eNOS/iNOS) pathway in a rat model. METHODS: Sprague-Dawley rats were subjected to 60 min of coronary artery occlusion (or sham procedure) followed by 2 h of reperfusion and were then divided into treatment groups: sham, model, DL (500 mg/kg), DL (500 mg/kg) + eNOS inhibitor L-nitroarginine (L-NNA; 7.5 mg/kg), and sodium nitroprusside (SNP; 0.5 mg/kg). There were 16 per group. Areas of no-reflow were determined by thioflavin S staining of heart tissue. Cardiac function was assessed by echocardiography. Myocardial enzymes and antioxidants in serum were measured and analyzed. The relative protein expression levels of eNOS and iNOS were determined by western blotting. RESULTS: DL had a myocardial protective effect on myocardial reperfusion and reduced the area of no-reflow. The serum levels of creatine kinase (CK), myocardial CK isoenzyme CK-MB, and lactate dehydrogenase were significantly lower in the DL group than in the model (P < 0.05). DL treatment also decreased the serum content of malondialdehyde and reactive oxygen species (ROS), increased the activity of superoxide dismutase and nitric oxide, and promoted eNOS expression (P < 0.05) while lowering iNOS expression. CONCLUSION: DL reduced the area of no-reflow and had a myocardial protective effect that may be associated with the eNOS/iNOS pathway.

A Network Pharmacology-Based Approach to Investigating the Mechanisms of Fushen Granule Effects on Intestinal Barrier Injury in Chronic Renal Failure.

PURPOSE: Fushen Granule (FSG) is a Chinese medicine prepared by doctors for treating patients with chronic renal failure, which is usually accompanied by gastrointestinal dysfunction. Here, we explore the protective effect of FSG on intestinal barrier injury in chronic renal failure through bioinformatic analysis and experimental verification. METHODS: In this study, information on the components and targets of FSG related to CRF is collected to construct and visualize protein-protein interaction networks and drug-compound-target networks using network pharmacological methods. DAVID is used to conduct gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Then, it is validated by in vitro experiments. In this study, the human intestinal epithelial (T84) cells are used and divided into four groups: control group, model group, FSG low-dose group, and FSG high-dose group. After the experiment, the activity of T84 cells is detected by a MTT assay, and the expressions of tight junction protein ZO-1, claudin-1, nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), malondialdehyde (MDA), and cyclooxygenase-2 (COX-2) are examined by immunofluorescence and/or western blotting. RESULTS: Eighty-six potential chronic renal failure-related targets are identified by FSG; among them, nine core genes are screened. Furthermore, GO enrichment analysis shows that the cancer-related signaling pathway, the PI3K-Akt signaling pathway, the HIF1 signaling pathway, and the TNF signaling pathway may play key roles in the treatment of CRF by FSG. The MTT method showed that FSG is not cytotoxic to uremic toxin-induced injured T84 cells. The results of immunofluorescence and WB indicate that compared with the control group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is decreased and protein expressions level of HO-1, MDA, and COX-2 is increased after urinary toxin treatment. Instead, compared with the model group, protein expressions level of ZO-1, claudin-1, and Nrf2 in T84 cells is increased and protein expressions level of HO-1, MDA, and COX-2 is decreased after FSG treatment. CONCLUSION: FSG had a protective effect on urinary toxin-induced intestinal epithelial barrier injury in chronic renal failure, and its mechanism may be related to the upregulation of Nrf2/HO-1 signal transduction and the inhibition of tissue oxidative stress and inflammatory responses. Screening CRF targets and identifying the corresponding FSG components by network pharmacological methods is a practical strategy to explain the mechanism of FSG in improving gastrointestinal dysfunction in CRF.

Lentinan combined with cisplatin for the treatment of non-small cell lung cancer.

BACKGROUND: A growing number of studies suggest that lentinan combined with cisplatin thoracic injection for the treatment of lung cancer is an effective combination of traditional Chinese and Western medicine, which has a continuous and beneficial effect on eliminating clinical symptoms and improving cachexia in lung cancer patients. However, whether this treatment is effective and safe for lung cancer patients or not, evidence supporting the effectiveness and safety of this treatment is still incomplete. Besides, there is lack of systematic review to assess the detailed situation (including risk of bias and methodology) of current related clinical studies. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of lentinan combined with cisplatin thoracic injection in the treatment of lung cancer. METHODS: The major databases (Embase, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database [VIP] Database, Chinese Biomedical Literature Service System [SinoMed], and Wanfang Database) were searched from inception to March 1, 2020. Randomized controlled trials (RCTs) of lentinan combined with cisplatin chest injection on patients with non-small cell lung cancer (NSCLC) were identified. Two assessors reviewed each trial independently. The methodological quality of the eligible studies was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Both the data extraction and the literature quality screening evaluation were conducted independently by 2 researchers. RESULTS: Totally 17 clinical RCTs were included in this study, involving 1390 patients. Meta-analysis results showed that the clinical efficacy (risk ratio [RR] = 1.34, 95% confidence interval [CI] 1.21-1.48), effective subgroup analysis (RR = 1.51, 95% CI 1.3-1.77), and quality of life (RR = 1.48, 95% CI 1.27-1.72), the differences are statistically significant. In terms of adverse reactions, mainly related to gastrointestinal reactions and bone marrow suppression, the incidence and degree of adverse reactions of lentinan combined with cisplatin thoracic injection group were lower than those of cisplatin thoracic injection group alone. CONCLUSIONS: The current evidence prompted that Lentinan combined with cisplatin in thoracic injection might benefit patients with NSCLC on a certain extent; this systematic review revealed some definite conclusions about the application of Lentinan combined with cisplatin in thoracic injection for NSCLC. Due to the low methodological quality, high risk of bias, and inadequate reporting on clinical data, these results still require verification by a large number of well designed, heterogeneous RCT studies. More rigorous, multicenter, sufficient-sample, and double-blind RCTs are warranted.

[Study on different ploidy Siraitia grosvenorii and their genetic relationship by FTIR].

Siraitia grosvenorii was an important Chinese traditional medicine. The spectra of leaf of diploid, triploid and tetraploid Siraitia grosvenorii were determined by Fourier transform infrared spectroscopy (FTIR) with OMNI sampler directly, fast and accurately. And based on the indices of wave number-absorbance from different bands and through comparison of differences of these infrared spectra the ploidy difference and genetic relationship of Siraitia grosvenorii were studied by the methods of principal component analysis (PCA) and cluster analysis. The results showed that for the ploidy, the position relationship of PCA three-dimensional-plot and the distance coefficient of clustering analysis plot between diploid and tetraploid were most remarkbly different, and the triploid was basically between diploid and tetraploid, so the ploidy was more different, the position relationship of PCA and the distance coefficient of clustering analysis were further, and the law was: 2 X < 3 X < 4 X. At the same time, the genetic relationship was further with each other while the position relationship of PCA and distance coefficient of clustering analysis was further too. And the genetic relationship of triploid was affected by the different male parent while their female parent was the same one. Therefore, using FTIR based on PCA and cluster analysis we could reveal the difference of ploidy and the genetic relationship between Siraitia grosvenorii to a certain extent. FTIR could be used for excellently polyploidy species breeding of Siraitia grosvenorii.