Xiaoer niuhuang qingxin powder alleviates influenza a virus infection by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoer Niuhuang Qingxin Powder (XNQP) is a classic traditional Chinese medicine formula with significant clinical efficacy for treating febrile convulsions and influenza. AIM OF THE STUDY: This study aims to explore the potential mechanisms of XNQP in combating combating the influenza A virus, providing a theoretical basis for its clinical application. MATERIALS AND METHODS: The present investigation employed network pharmacology and bioinformatics analysis to determine the TLR4/MyD88/NF-κB signaling pathway as a viable target for XNQP intervention in IAV infection.Subsequently, a mouse model of influenza A virus infection was established, and different doses of XNQP were used for intervention. The protein expression levels of TLR4/MyD88/NF-κB were detected using HE staining, Elisa, immunohistochemistry, immunofluorescence, and western blot. RESULTS: The results showed that treatment with XNQP after IAV infection reduced the mortality and prolonged the survival time of infected mice. It reduced the release of TNF-α and IFN-γ in the serum and alleviated pathological damage in the lung tissue following infection. Additionally, the levels of TLR4, MyD88, NF-κB, and p-NF-κB P65 proteins were significantly reduced in lung tissue by XNQP. The inhibitory effect of XNQP on the expression of MyD88 and NF-κB was antagonized when TLR4 signaling was overexpressed. Consequently, the expression levels of MyD88, NF-κB, and p-NF-κB P65 were increased in lung tissue. Conversely, the expression levels of the proteins MyD88, NF-κB, and p-NF-κB P65 were downregulated when TLR4 signaling was inhibited. CONCLUSIONS: XNQP alleviated lung pathological changes, reduced serum levels of inflammatory factors, reduced mortality, and prolonged survival time in mice by inhibiting the overexpression of the TLR4/MyD88/NF-κB signaling pathway in lung tissues after IAV infection.

Research progress on the mechanism of traditional Chinese medicine regulating intestinal microbiota to combat influenza a virus infection.

Influenza A viruses (IAV) are a prevalent respiratory pathogen that can cause seasonal flu and global pandemics, posing a significant global public health threat. Emerging research suggests that IAV infections may disrupt the balance of gut microbiota, while gut dysbiosis can affect disease progression in IAV patients. Therefore, restoring gut microbiota balance may represent a promising therapeutic target for IAV infections. Traditional Chinese medicine, with its ability to regulate gut microbiota, offers significant potential in preventing and treating IAV. This article provides a comprehensive review of the relationship between IAV and gut microbiota, highlighting the impact of gut microbiota on IAV infections. It also explores the mechanisms and role of traditional Chinese medicine in regulating gut microbiota for the prevention and treatment of IAV, presenting novel research avenues for traditional Chinese medicine-based IAV treatments.

Clinical Effect of Rehabilitation New Fluid Combined with Sanjie Analgesic Capsules in the Treatment of Granulomatous Mastitis and Thyroiditis and Impact on Immune Indexes of Patients.

Objective: To analyze the clinical effect of rehabilitation new fluid combined with Sanjie analgesic capsules in the treatment of granulomatous lobular mastitis (GLM) and thyroiditis and the impact on immune indexes of patients. Methods: For a retrospective study, we selected 150 patients with GLM and 150 patients with thyroiditis admitted to The Fourth Hospital of Shijiazhuang from January 2021 to January 2022. We divided them into three groups based on the treatment methods. Control group 1 (CG1) included patients treated with rehabilitation new fluid alone, while control group 2 (CG2) included patients treated with the Sanjie analgesic capsules alone. The third group, the observation group (OG), included patients treated with rehabilitation new fluid (extract of drying body from Periplaneta americana) at an oral dose of 10 ml combined with Sanjie analgesic capsules. There were 50 patients in each group. The clinical efficacy, symptom improvement, the level changes of free triiodothyronine (FT3), free tetraiodothyronine (FT4), and thyroid stimulating hormone (TSH), and the changes of immune indexes such as CD4+ (cluster of differentiation 4+), CD25+ (cluster of differentiation 25+), CD68+ (cluster of differentiation 68+) and CD138+ (cluster of differentiation 138+) were analyzed. Results: After treatment, the total treatment effectiveness of GLM in the OG was 94%, which was significantly higher than 80% in the CG1 and 78% in the CG2 (P = .037, .021), while the total treatment effectiveness of thyroiditis in the OG was 92%, which was significantly higher than 76% in the CG1 and 74% in the CG2 (P = .029, 0.017). The scores of breast pain, breast overflow, tumor size, local skin changes, and axillary fossa lymphadenectasis of the affected side in the OG of GLM were better than those in CG1 (Pbreast pain < .001, 95%CI: 0.573-1.747; Pbreast overflow = .022, 95%CI: 0.074-0.905; Ptumor size = .008, 95%CI: 0.231-1.489; Plocal skin changes = .001, 95%CI: 0.382-1.498; Paxillary fossa lymphadenectasis of the affected side = .011, 95%CI: 0.096-0.704) and CG2 (Pbreast pain = .001, 95%CI: 0.449-1.711; Pbreast overflow = .049, 95%CI: 0.002-0.798; Ptumor size =0.019, 95%CI: 0.132-1.428; Plocal skin changes < .001, 95%CI: 0.563-1.517; Paxillary fossa lymphadenectasis of the affected side = .001, 95%CI: 0.202-0.678). The levels of FT3 and FT4 in the OG of thyroiditis were higher than CG1 (PFT3 < .001, 95%CI: 0.951-1.590; PFT4 < .001, 95%CI: 1.421-2.618) and CG2 (PFT3 < .001, 95%CI: 0.943-1.643; PFT4 < .001, 95%CI: 1.521-2.758), and the TSH level was lower compared with CG1 (PTSH < .001, 95%CI: 2.409-3.070) and CG2 (PTSH < .001, 95%CI: 2.540-3.230). The immune indexes of GLM were improved, and the levels of CD4+, CD25+, CD68+, and CD138+ in the OG were better than those in the CG1 (PCD4+ < .001, 95%CI: 2.967-4.912; PCD25+ < .001, 95%CI: 3.707-5.212; PCD68+ < .001, 95%CI: 1.445-2.200; PCD138+ < .001, 95%CI: 3.922-5.510) and CG2 (PCD4+ < .001, 95%CI: 3.093-4.995; PCD25+ < .001, 95%CI: 3.527-4.904; PCD68+ < .001, 95%CI: 1.334-2.216; PCD138+ < .001, 95%CI: 3.878-5.352). The immune indexes of thyroiditis were improved, and the levels of CD4+, CD25+, CD68+, and CD138+ in the OG were better than those in the CG1 (PCD4+ < .001, 95%CI: 4.235-6.117; PCD25+ < .001, 95%CI: 3.300-4.810; PCD68+ < .001, 95%CI: 1.173-1.939; PCD138+ < .001, 95%CI: 3.704-4.881) and CG2 (PCD4+ < .001, 95%CI: 3.136-5.422; PCD25+ < .001, 95%CI: 3.182-4.615; PCD68+ < .001, 95%CI: 1.216-2.113; PCD138+ < .001, 95%CI: 4.145-5.527). Conclusion: The clinical effect of rehabilitation new fluid combined with Sanjie analgesic capsule in the treatment of GLM and thyroiditis is remarkable, which enables enhancement of the treatment efficiency, and improves patients' clinical symptoms, functional indexes, and the levels of immune indexes, as a direction for the follow-up treatment in the clinic.

Progress on traditional Chinese medicine in treatment of ischemic stroke via the gut-brain axis.

Ischemic stroke is a common issue that severely affects the human health. Between the central nervous system and the enteric system, the " Gut-Brain " axis, the bidirectional connection involved in the neuro-immuno-endocrine network, is crucial for the occurrence and development of ischemic stroke. Ischemic stroke can lead to change in the gut microbiota and gastrointestinal hormones, which will then reversely affect the disease development. Traditional Chinese Medicine (TCM) has unique advantages with reference to the treatment for ischemic stroke. The latest research revealed that a significant portion of medicines and prescriptions of TCM exert their therapeutic effects by improving the gut microbiota and regulating the secretion of gastrointestinal hormones. The present review summarized the Chinese medicines that play a therapeutic role in cerebral ischemia through regulating the "Gut-Brain" axis and described the corresponding mechanisms. This study attempts to provide reference for clinical selection of Chinese medicines and helps better understand the relevant mechanisms of action.

Deciphering the pharmacological mechanisms of Chaenomeles Fructus against rheumatoid arthritis by integrating network pharmacology and experimental validation.

Chaenomeles Fructus is a plant that can be used for both food and medicine. Modern studies have shown that Chaenomeles Fructus has anti-inflammatory and immunosuppressive effects on arthritis. However, the mechanism of action of Chaenomeles Fructus on rheumatoid arthritis (RA) and its main active ingredients are still unclear. This study was aimed at devising an integrated strategy for investigating the bioactivity constituents and possible pharmacological mechanisms of Chaenomeles Fructus against RA. The components of Chaenomeles Fructus were analyzed using UPLC-Q-Exactive orbitrap MS techniques and applied to screen the active components of Chaenomeles Fructus according to their oral bioavailability and drug-likeness index. Then, we speculated on the potential molecular mechanisms of Chaenomeles Fructus against RA through a network pharmacology analysis. Finally, the potential molecular mechanisms of Chaenomeles Fructus against RA were validated in a complete Freund's adjuvant (CFA)-induced RA rat model. We identified 48 components in Chaenomeles Fructus and screened seven bioactive ingredients. The results of the network pharmacology prediction and the experimental verification results were analyzed by Venn analysis, and the experimental results concluded that Chaenomeles Fructus mainly interferes with the inflammation of RA by inhibiting arachidonic acid metabolism and the MAPK signaling pathway. This study identified the ingredients of Chaenomeles Fructus by UPLC-Q-Exactive orbitrap MS and explained the possible mechanisms of Chaenomeles Fructus against RA by integrating network pharmacology and experimental validation.

Research progress on classical traditional Chinese medicine Taohong Siwu decoction in the treatment of coronary heart disease.

The pathogenesis of coronary heart disease is closely related to blood stasis. Taohong Siwu decoction (THSW for short) is one of the most widely used prescriptions for activating blood and removing stasis. Clinical research has confirmed its curative effect on coronary heart disease. However, its underlying mechanism remains unclear. Therefore, this paper reviewed the clinical efficacy of THSW and determine its effective components based on a comprehensive literature review. Furthermore, the core components and targets of THSW in treating coronary heart disease using molecular docking were verified, and the interaction sites were predicted to construct a theoretical basis for the clinical application of THSW.

Analysis of Relevant Factors Affecting the Pregnancy Rate of Frozen-Thawed Embryo Transfer Cycle.

Objective: The aim of this study is to explore the relevant factors affecting the pregnancy rate of frozen-thawed embryo transfer cycle. Methods: The clinical data of 931 patients who underwent artificial cycle preparation for endometrial FET from April 2017 to November 2020 in the reproductive center of our hospital were retrospectively analyzed. Results: According to the pregnancy situation, the patients were divided into 450 cases of pregnancy and 481 cases of biochemical pregnancy. The univariate analysis of FET biochemical pregnancy showed that there were statistically significant differences between pregnancy and biochemical pregnancy in terms of years of infertility, age, endometrial thickness, P level, E2/P, and the number of high-quality embryos (P < 0.05). Multivariate analysis of pregnancy showed that age <30 years was a protective factor for biochemical pregnancy and endometrial thickness <8 mm and E2/P < 0.3 were risk factors (P < 0.05). Conclusion: The regulation of endometrial thickness and E2/P serves as the key of treatment for patients undergoing FET using artificial cycle preparation for endometrial transfer, and it contributes to improve the pregnancy rate; also, the patient's age is an important indicator influencing the pregnancy rate.

Molecular Mechanism of Polysaccharides Extracted from Chinese Medicine Targeting Gut Microbiota for Promoting Health.

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity, type 2 diabetes mellitus, heart failure, and non-alcoholic fatty liver disease. Polysaccharides extracted from Chinese medicine (CM) can not only alleviate pathological status but also promote health by anti-inflammatory, regulating immunity, lowering blood glucose and lipids, anti-cancer, and anti-oxidation. The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment. In addition, they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota. This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics for promoting health.

Clinical application and pharmacological mechanism of Wuling powder in the treatment of ascites: A systematic review and network pharmacological analysis.

Ascites is one of the common complications in patients with decompensated liver cirrhosis and liver cancer. Wuling powder (WLP) is a classic prescription for the treatment of water retention caused by bladder gasification. It is also widely used in the treatment of ascites. This systematic review aimed to evaluate the clinical efficacy of WLP and determine its effective chemical components based on a large number of related pieces of literature. The pharmacological effects and chemical constituents of WLP were summarized. Besides, the clinical research status of WLP in the treatment of ascites caused by liver cancer and cirrhosis was analyzed. The key targets and pathways of WLP in the treatment of ascites based on network pharmacology analysis were also discussed. Furthermore, the core components and core targets of WLP in the treatment of ascites using molecular docking were verified and the interaction sites were predicted, to provide a theoretical and scientific basis for the clinical application of WLP.

Integrated analysis of the chemical-material basis and molecular mechanisms for the classic herbal formula of Lily Bulb and Rehmannia Decoction in alleviating depression.

BACKGROUND: Lily Bulb and Rehmannia Decoction (LBRD), is a traditional Chinese formula that has been shown to be safe and effective against depression; however, its material basis and pharmacological mechanisms remain unknown. METHODS: Here, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and high-performance liquid chromatography (HPLC) were used to identify the chemical spectrum and qualitatively identify the major active ingredients in the LBRD standard decoction, respectively. Subsequently, we assessed the behavior, neuronal function and morphology, neurotransmitter levels, hypothalamic-pituitary-adrenal (HPA)-axis associated hormones, inflammatory cytokine levels, and miRNA/mRNA expression alterations in an in vitro/vivo depression model treated by the LBRD standard decoction. Finally, miRNA/mRNA regulatory networks were created through bioinformatics analysis, followed by functional experiments to verify its role in LBRD standard decoction treatment. RESULTS: A total of 32 prototype compounds were identified in the LBRD standard decoction, and the average quality of verbascoside in the fresh lily bulb decoction, fresh raw Rehmannia juice, and the LBRD standard decoction were 0.001264%, 0.002767%, and 0.009046% (w/w), respectively. Administration of the LBRD standard decoction ameliorated chronic unpredictable mild stress (CUMS)-induced depression-like phenotypes and protected PC12 cells against chronic corticosterone (CORT)-induced injury. The levels of neurotransmitter, cytokine, stress hormones and neuronal morphology were disrupted in the depression model, while LBRD standard decoction could work on these alterations. After LBRD standard decoction administration, four differentially expressed miRNAs, rno-miR-144-3p, rno-miR-495, rno-miR-34c-5p, and rno-miR-24-3p, and six differentially expressed mRNAs, Calml4, Ntrk2, VGAT, Gad1, Nr1d1, and Bdnf overlapped in the in vivo/vitro depression model. Among them, miR-144-3p directly mediated GABA synthesis and release by targeting Gad1 and VGAT, and miR-495 negatively regulated BDNF expression. The LBRD standard decoction can reverse the above miRNA/mRNA network-mediated GABA and BDNF expression in the in vivo/vitro depression model. CONCLUSION: Collectively, the multi-components of the LBRD standard decoction altered a series of miRNAs in depression through mediating GABAergic synapse, circadian rhythm, and neurotrophic signaling pathway etc., thereby abolishing inhibitory/excitatory neurotransmitter deficits, recovering the pro-/anti-inflammatory cytokine levels and regulating the HPA-axis hormone secretion to achieve balance of the physiological function of the whole body.

First Report of Root Rot Caused by the Fusarium oxysporum Species Complex on Codonopsis pilosula in China.

Codonopsis pilosula Franch., also known as Dangshen, is an important medicinal plant in China. It is widely cultivated for a major income of local farmers in Dingxi, Gansu Province. Its dried roots have the effects of supplementing vital energy, nourishing spleen and lung, enhancing organic immunity, helping depressurization, and improving microcirculation, etc., for humans. In June to October, 2018-2020, root rot disease was observed on C. pilosula with incidences up to 20% in the Dingxi region. We collected ten diseased and healthy plants from Dingxi (35°06'N, 104°29'E, 2206 m a.s.l.) in October 2019. The rotting root tissues were sterilized with 70% ethanol for 30 s and 3% NaOCl for 5 min and placed on potato dextrose agar (PDA) plates incubated at 25℃to isolate the pathogen (Shang et al. 2014). From the similar fungal cultures isolated after 7 days on PGA, isolate B17 was purified for morphological and molecular characterization. Its colony appeared light purple and produced long aerial hyphae. Slightly curved macroconidia (12.3 to 31.7 × 3.1 to 5.1 µm, n=40) and oval-ellipsoid and cylindrical microconidia (6.1 to 9.9 × 2.8 to 4.5 µm, n=30) were observed. The internal transcribed spacer region (ITS) and the translation elongation factor-1 alpha (TEF-1α) gene were amplified using primers ITS1/ITS4 and EF-1/EF-2 (Uwaremwe et al. 2020), respectively. The 489 bp (ITS) and 631 bp (TEF-1α) sequences were deposited in GenBank (Accession No. MN744360 and MN786974, respectively). The ITS sequence had 100% homology to isolate JJF2 (No. MN626452, ITS) (Ma et al. 2020), and the TEF-1α sequence had 100% homology to isolate Fo353 (No. KM065860) (Koyyappurath et al. 2016) of Fusarium oxysporum Schlecht. emend. Snyder & Hansen, which caused root rot of Panax ginseng and Vanilla planifolia, respectively. A phylogenetic tree was generated using the unweighted pair-group method with arithmetic average in the MycoBank database (O'Donnell et al. 2015), which clustered isolate B17 in the F. oxysporum species complex. Twenty 1-year-old plants of C. pilosula were inoculated with were inoculated by dipping the washed roots in a conidial suspension (2 ×106 conidia/ml added with 0.2% Tween 20) for 20 min before transplanted into pots (16 × 16 × 23 cm) with four plants per pot filled with sterilized peat and soil mixture (2:1 v/v) and grown in a greenhouse at 26oC with >70% humidity and 16 h light. Sterilized water added with 0.2% Tween 20 was used as a control. One week after inoculation, the leaves of pathogen-inoculated plants became yellow, and wilting occurred at the leaf tips 18 days later. Some of the inoculated plants died 45 days after inoculation, and the low part of roots had dark brown to black lesions and became rotting. The control plants did not show symptoms. The pathogenicity test was repeated three times with the same fungus isolated from the infected root tissue. To the best of our knowledge, this is the first report that F. oxysporum causes root rot on C. pilosula in China. F. oxysporum is a serious threat to C. pilosula cultivation, and the finding of this pathogen provides a clear target for root rot control.

Coix lacryma-jobi Seed Oil Reduces Fat Accumulation in Nonalcoholic Fatty Liver Disease by Inhibiting the Activation of the p-AMPK/SePP1/apoER2 Pathway.

The lipid metabolism disorder is the key role of Nonalcoholic fatty liver disease (NAFLD). Selenoprotein P plays an important role in the pathological process of lipid accumulation. Coix lacryma-jboi seed oil (CLSO) is an active component extracted from Coix lacryma-jobi seed (CLS) which has been found to be effective of reducing blood fat and antioxidative. But the effect and mechanism of CLSO on NAFLD are not clear. The aim of this study was to explore the therapeutic effect and mechanism of CLSO in the treatment of NAFLD. Our result showed that CLSO decreased the liver/body weight ratio, lowered the total cholesterol (TC) and triacylglycerol (TG), and elevated the high density lipoprotein (HDL) in serum. CLSO reduced the lipid deposition in the liver of NAFLD rats. In addition, CLSO could bring down the abnormal expression of superoxide dismutase (SOD) and malondialdehyde (MDA). Moreover, CLSO significantly declined the liver apolipoprotein E (apoE), apolipoprotein E receptor (apoER) and selenoprotein P 1 (SePP1) expression. In vivo, CLSO decreased the lipid droplets and TG level, reduced the protein expression of SePP1, apoER, phosphor-adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) in the cytoplasm of HepG2 cells induced by oleic acid and palmitic acid (OP). At the same time, lipid accumulation was observed in the Sepp1 high expression cells induced by endoplasmic reticulum (ER) activator tunicamycin (Tm). CLSO could identically reduce the protein expression of SePP1, apoER, p-AMPK in the cytoplasm of HepG2 cells induced by Tm. This result not only proved the CLSO had therapeutic effect on NAFLD, but also confirmed its mechanism associated with degrading the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) which led to the decrease of the expression SePP1/apoER2 in order to reduce lipid accumulation. The study suggests CLSO has great medicinal value in treating NAFLD besides its edibility.

Research progress on the pharmacological effect and clinical application of Tongqiao Huoxue Decoction in the treatment of ischaemic stroke.

Ischaemic stroke (IS) is a common type of stroke characterised by sudden fainting and communication disorders, alongside a number of other symptoms. It is characterised by high morbidity, disability, and mortality rates. Tongqiao Huoxue Decoction (THD) is effective in the treatment of stroke. As a representative prescription for promoting blood circulation and removing blood stasis, THD has been widely used clinically. This paper systematically introduces clinical and experimental studies of THD in the treatment of IS, summarising its clinical application, pharmacological mechanisms, and active components in the treatment of IS. It also explores its key pathways in the treatment of IS through network pharmacology analyses, thereby speculating on its underlying mechanisms. It is of great significance for the secondary development of this classic prescription as well as for the research and development of new drugs.

GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice.

The G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A-/-) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A-/- mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A-/- mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A-/- mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/ß-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/ß-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A-/- mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.

From the perspective of Traditional Chinese Medicine: Treatment of mental disorders in COVID-19 survivors.

PURPOSE: The aim of this study is to explore the possible benefits of traditional Chinese medicine on the pathogenesis of psychological and mental health of COVID-19 survivors. METHODS: A literature search was conducted to confirm the effects of COVID-19 on psychological and mental health of survivors. In addition to this, on the basis of signs and symptoms, TCM were used on treat mental disorder as per suggested clinical and animal experimental data plus relevant records in classical Chinese medicine books written by Zhang Zhongiing during Han Dynasty. A series of treatment plans were prescribed for COVID-19 survivors with psychological and mental disorders. RESULTS: According to previous extensive studies focusing on effects on mental health of survivors, high incidence was observed in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) survivors. During investigations of mental health of COVID-19 patients and survivors, it is observed that they also had symptoms of mental disorders and immune dysfunction. Furthermore, it was also proposed that depression, anxiety and post-traumatic stress disorder (PTSD) were most common mental disorders requiring special attention after the recovery from COVID-19. The symptoms of COVID-19 were analyzed, and the TCM syndrome of the depression, anxiety and PTSD after recovered from COVID19 was interpreted as internal heat and Yin deficiency. These three mental disorders pertains the category of "Lily disease", "hysteria" and "deficient dysphoria" in TCM. CONCLUSION: Lily Bulb, Rhizoma Anemarrhena Decoction and Ganmai Dazao Decoction were used to treat depression. Suanzaoren Decoction, Huanglian Ejiao Decoction and Zhizi Chi Decoction were suggested for anxiety. Moreover, Lily Bulb, Rehmannia Decoction and Guilu Erxian Decoction were the formula for PTSD.

Zi Shen Huo Luo Formula Prevents Aldosterone-Induced Cardiomyocyte Hypertrophy and Cardiac Fibroblast Proliferation by Regulating the Striatin-Mediated MR/EGFR/ERK Signaling Pathway.

Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) is an important factor in the development of hypertension. Excessive aldosterone can lead to myocardial extracellular matrix collagen proliferation, fibrosis, and cardiomyocyte hypertrophy and aggravate maladaptive remodeling. The results of our previous clinical and animal experiments suggested that Zi Shen Huo Luo Formula (ZSHLF) combined with perindopril can effectively control the process of left ventricular hypertrophy (LVH). The purpose of this study was to investigate whether ZSHLF-treated serum inhibits the membrane localization of the striatin-mediated mineralocorticoid receptor (MR) and affects MR-mediated nongenomic effects and the downstream epidermal growth factor receptor (EGFR)/extracellular regulated kinase (ERK) signaling pathways, thereby improving aldosterone-induced myocardial remodeling. Serum containing ZSHLF was prepared and used to treat rat cardiomyocytes and cardiac fibroblasts in vitro after aldosterone induction and striatin knockdown by small interfering RNA (siRNA). Cell-based assays were carried out to determine the cardiomyocyte surface area and assess the proliferation rate and hydroxyproline secretion of cardiac fibroblasts. Quantitative real-time PCR (qRT-PCR), immunoprecipitation (IP), and Western blotting were performed to evaluate the striatin-mediated MR/EGFR/ERK signaling pathway. In the present study, ZSHLF attenuated the aldosterone-induced hypertrophy of cardiomyocytes and inhibited the proliferation and collagen synthesis of cardiac fibroblasts. ZSHLF also reduced striatin mRNA expression and inhibited striatin and MR binding, membrane MR protein expression, and EGFR and ERK1/2 phosphorylation. Furthermore, after striatin silencing with siRNA, some of the effects of ZSHLF were not changed significantly. In conclusion, ZSHLF inhibits the downstream EGFR/ERK signaling pathway by blocking the striatin-mediated membrane localization of MR, which may be an important molecular mechanism by which ZSHLF improves aldosterone-induced myocardial remodeling.

Chinese herbal medicine Baoyuan Jiedu decoction inhibits the accumulation of myeloid derived suppressor cells in pre-metastatic niche of lung via TGF-ß/CCL9 pathway.

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-ß, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-ß/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-ß/CCL9 pathway.

Zi Shen Huo Luo Formula Enhances the Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors on Hypertensive Left Ventricular Hypertrophy by Interfering With Aldosterone Breakthrough and Affecting Caveolin-1/Mineralocorticoid Receptor Colocalization and Downstream Extracellular Signal-Regulated Kinase Signaling.

Left ventricular hypertrophy (LVH) is an important characteristic of hypertensive heart disease. Renin-angiotensin system (RAS) blockers have been shown to be effective drugs for the reversal of LVH. Clinical and experimental studies have shown that Zi Shen Huo Luo Formula (ZSHLF) can improve the efficacy of perindopril in the treatment of hypertensive LVH, but its mechanism is unclear. This study aimed to investigate the possible mechanism to improve the efficacy of perindopril. First, we identified 23 compounds in ZSHLF by ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analysis, among which ferulic acid, caffeic acid, vanillic acid, berberine, rutin, quercetin, kaempferol, stachydrine, and tiliroside have been reported to reduce blood pressure and exhibit cardioprotective effects. Second, we treated spontaneously hypertensive rats (SHRs) with perindopril and ZSHLF for 12 continuous weeks and found that chronic use of perindopril could increase the aldosterone (ALD) levels and cause aldosterone breakthrough (ABT). ZSHLF combined with perindopril reduced the ALD levels, interfered with ABT, decreased blood pressure, improved left ventricular diastolic dysfunction, and decreased the collagen volume fraction; these effects were superior to those of perindopril alone. In vitro experiments, ALD-induced cardiomyocytes (H9c2 cells) and cardiac fibroblasts were treated with ZSHLF-containing serum, which suppressed ALD-induced cardiomyocyte hypertrophy and cardiac fibroblast proliferation, increased mineralocorticoid receptor (MR) and Cav-1 colocalization and decreased phosphorylated epidermal growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase (pERK) protein expression the cells. In conclusion, ZSHLF can interfere with ABT and affect the pathological role of ALD by affecting MR and Cav-1 interactions and EGFR/ERK signaling pathway. These effects represent a possible mechanism by which ZSHLF improves the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in hypertensive LVH treatment. However, the major bioactive components or metabolites responsible for the effects and the implications of these findings in patients need further verification.

Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress-induced depression-like behavior.

According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of "lily disease", the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High-performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme-linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ-aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural-immunity. GABAergic and glutamatergic synapses as well as brain-derived neurotrophic factor (BDNF)/TrkB-dependent phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin-1 (mTOR1), might be the main signaling pathways underlying the multi-target therapeutic effects of LBRD against depression.

[Acupuncture up-regulates MCT2 expression of peri-ischemic cortex in middle cerebral artery occlusion rats].

OBJECTIVE: To observe the effect of manual acupuncture (MA)＋ electroacupuncture (EA) on changes of neurological function and expression of monocarboxylate transporter 2(MCT2)in cerebral ischemia (CI) rats, so as to explore its mechanism underlying improvement of ischemic cerebrovascular disease. METHODS: Eighty male Wistar rats were equally randomized into four groups: normal control (normal), sham operation (sham), model and acupuncture. The CI model was induced by middle cerebral artery occlusion (MCAO) with a thread embolus. Manual acupuncture stimulation (mild twisting reinforcing-reducing method) was applied to "Baihui"(GV20)and "Fengfu"(GV16) for 10 min. EA (1 mA, 2 Hz /15 Hz) was respectively applied to bilateral "Quchi" (LI11) and "Zusanli"(ST36) for 20 min, once per day for 7 days. The neurological deficit severity was evaluated according to Zea Longa's methods. The activity of lactate dehydrogenase (LDH), fructose-6-phosphate kinase (PFK) and pyruvate kinase (PK) in the peri-ischemic cortex tissue was detected by enzymatic chemistry, and the expression of MCT2 detected by immunofluorescence histochemistry, Western blot and quantitative real-time PCR, separately. RESULTS: After CI and in comparison with the normal and sham groups, the Zea Longa's score, the fluorescence intensity and the expression level of MCT2 protein were significantly increased (P<0.01), and the activity of LDH, PFK and PK in the peri-ischemic cortex was significantly decreased in the model group (P<0.01). There was no significant change in the relative expression of MCT2 mRNA (P>0.05). Following the intervention and in comparison with the model group, the Zea Longa's score was considerably decreased in the acupuncture group (P<0.01), the activity of LDH, PFK and PK，and the expression levels of MCT2 protein and mRNA were considerably or further up-regulated in the acupuncture group (P<0.01, P<0.05). CONCLUSION: Acupuncture intervention can improve neurological function in CI rats, which is possibly related with its effects in up-regulating the expression of MCT2 and promoting the utilization of lactate in peri-ischemic cortex.