Multi-metabolomics and intestine microbiome analysis: YZC extract ameliorates septic-ALI by modulating intestine microbiota to reduce TMAO/NLRP3 signaling.

BACKGROUND: Sepsis causes inflammation in response to infection, often leading to acute lung injury (ALI). Yazhicao (Commelina communis L., YZC) is widely distributed in the global tropics and has good anti-respiratory inflammatory activity; however, the protection of YZC against septic-ALI has not been established. PURPOSE: The role of YZC in septic-ALI will be investigated in this study. METHODS AND RESULTS: In this study, YZC was shown to inhibit excessive inflammation and alleviate septic-ALI. Network pharmacology predicts that Quercetin, Acacetin and Diosmetin have the potential to serve as the pharmacological substance basis of YZC in alleviating septic-ALI. The metabolomics results indicated that YZC could improve the metabolic disorders caused by septic-ALI, which were mostly concerned with energy metabolism and amino acid metabolism, with Trimethylamine (TMA)/Trimethylamine N-oxide (TMAO) being potential small molecule metabolic markers for the clinical diagnosis and treatment of septic-ALI. YZC inhibits the initiation and progression of septic-ALI by controlling the TMA/TMAO metabolites. Our results also suggest that YZC protects the intestinal barrier from damage. Furthermore, our research indicated that YZC reduces TMAO synthesis by inhibiting TMA production through remodeling the intestine microbiota. We investigated the mechanism of YZC-mediated protection against septic-ALI and showed that YZC reduced the expression of proteins associated with NLRP3 inflammatory vesicles in the lung by inhibiting the expression of NF-κB. CONCLUSION: These results show that YZC inhibits the NF-κB/NLRP3 signaling pathway by regulating metabolic and intestinal flora disorders in septic-ALI mice to reduce TMAO synthesis. This study presents a theoretical groundwork for the advancement of novel medications and clinical use of YZC to enhance septic-ALI and furnishes a theoretical rationale for regulating intestinal microbiota as a therapeutic instrument to treat sepsis and septic-ALI.

Genus Physalis L.: A review of resources and cultivation, chemical composition, pharmacological effects and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Physalis L. (Solanaceae) is commonly used in the treatment of dermatitis, leprosy, bronchitis, pneumonia, hepatitis and rheumatism in China and other Asian countries. AIM OF THE REVIEW: This article reviews the resources, cultivation, phytochemistry, pharmacological properties, and applications of Physalis L., and proposes further research strategies to enhance its therapeutic potential in treating various human diseases. MATERIALS AND METHODS: We conducted a systematic search of electronic databases, including CNKI, SciFinder and PubMed, using the term "Physalis L." to collect information on the resources, phytochemistry, pharmacological activities, and applications of Physalis L. in China during the past ten years (2013.1-2023.1). RESULTS: So far, a variety of chemical constituents have been isolated and identified from Physalis L. mainly including steroids, flavonoids, and so on. Various pharmacological activities were evaluated by studying different extracts of Physalis L., these activities include anti-inflammatory, antibacterial, antioxidant, antiviral, antineoplastic, and other aspects. CONCLUSION: Physalis L. occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant resources and cultivation, chemical composition, pharmacological effects and applications.

Anemarrhena asphodeloides Bunge total saponins ameliorate diabetic cardiomyopathy by modifying the PI3K/AKT/HIF-1α pathway to restore glycolytic metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the theory of traditional Chinese medicine (TCM), diabetic cardiomyopathy (DCM) belongs to the category of "Xiaoke disease" according to the symptoms, and "stasis-heat" is the main pathogenesis of DCM. The Chinese medicine Anemarrhena asphodeloides Bunge (AAB), as a representative of heat-clearing and engendering fluid, is often used clinically in the treatment of DCM. Anemarrhena asphodeloides Bunge total saponins (RATS) are the main bioactive components of AAB, the modern pharmacologic effects of RATS are anti-inflammatory, hypoglycemic, and cardioprotective. However, the potential protective mechanisms of RATS against DCM remain largely undiscovered. AIM OF THE STUDY: The primary goal of this study was to explore the effect of RATS on DCM and its mechanism of action. MATERIALS AND METHODS: Streptozotocin and a high-fat diet were used to induce DCM in rats. UHPLC/Q-TOF-MS was used to determine the chemical components of RATS. The degenerative alterations and apoptotic cells in the heart were assessed by HE staining and TUNEL. Network pharmacology was used to anticipate the probable targets and important pathways of RATS. The alterations in metabolites and main metabolic pathways in heart tissue were discovered using 1 H-NMR metabolomics. Ultimately, immunohistochemistry was used to find critical pathway protein expression. RESULTS: First of all, UHPLC/Q-TOF-MS analysis showed that RATS contained 11 active ingredients. In animal experiments, we found that RATS lowered blood glucose and lipid levels in DCM rats, and alleviated cardiac pathological damage, and decreased cardiomyocyte apoptosis. Furthermore, the study found that RATS effectively reduced inflammatory factor release and the level of oxidative stress. Mechanistically, RATS downregulated the expression levels of PI3K, AKT, HIF-1α, LDHA, and GLUT4 proteins. Additionally, glycolysis was discovered to be a crucial pathway for RATS in the therapy of DCM. CONCLUSIONS: Our findings suggest that the protective effect of RATS on DCM may be attributed to the inhibition of the PI3K/AKT/HIF-1α pathway and the correction of glycolytic metabolism.

Anti-aging activities of Rehmannia glutinosa Libosch. crude polysaccharide in Caenorhabditis elegans based on gut microbiota and metabonomic analysis.

Aging is a degenerative progress, accompanied by oxidative damage, metabolic disorders and intestinal flora imbalance. Natural macromolecular polysaccharides have shown excellent anti-aging and antioxidant properties, while maintaining metabolic and intestinal homeostasis. The molecular weight, monosaccharide composition, infrared spectrum and other chemical structure information of four Rehmannia glutinosa polysaccharides (RG50, RG70, RG90, RGB) were determined, and their free radical scavenging ability was assessed. Molecular weight and monosaccharide composition analysis exhibited that RG50 (2-72 kDa), RG70 (3.2-37 kDa), RG70 (3-42 kDa), and RGB (3.1-180 kDa) were heteropolysaccharide with significant different monosaccharide species and molar ratios. We found that RG70 had the best antioxidant activity in vitro and RG70 could enhance the antioxidant enzyme system of Caenorhabditis elegans, diminished lipofuscin and reactive oxygen species levels, up-regulate the expression of daf-16, skn-1 and their downstream genes, and down-regulate the expression of age-1. Metabolomics results showed that RG70 mainly influenced glycine, serine and threonine metabolism and citric acid cycle. 16S rRNA sequencing showed that RG70 significantly up-regulated the abundance of Lachnospiraceae_NK4B4_group, which were positively correlated with amino acid metabolism and energy cycling. These results suggest that RG70 may delay aging by enhancing antioxidant effects, affecting probiotics and regulating key metabolic pathways.

Physalis alkekengi L. var. franchetii combined with hormone therapy for atopic dermatitis.

Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese medicine, is primarily used for the clinical treatment of AD. In this study, a 2,4-dinitrochlorobenzene-induced AD BALB/c mouse model was established, and a comprehensive pharmacological method was used to determine the pharmacological effects and molecular mechanisms of PAF in the treatment of AD. The results indicated that both PAF gel (PAFG) and PAFG+MF (mometasone furoate) attenuated the severity of AD and reduced the infiltration of eosinophils and mast cells in the skin. Serum metabolomics showed that PAFG combined with MF administration exerted a synergistic effect by remodeling metabolic disorders in mice. In addition, PAFG also alleviated the side effects of thymic atrophy and growth inhibition induced by MF. Network pharmacology predicted that the active ingredients of PAF were flavonoids and exerted therapeutic effects through anti-inflammatory effects. Finally, immunohistochemical analysis confirmed that PAFG inhibited the inflammatory response through the ERß/HIF-1α/VEGF signaling pathway. Our results revealed that PAF can be used as a natural-source drug with good development prospects for the clinical treatment of AD.

Advances in traditional Chinese medicine for the treatment of chronic obstructive pulmonary disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and thus imposes heavy economic burden on patients, their families, and society. Furthermore, COPD seriously affects the quality of life of patients. The concept of "overall regulation" of traditional Chinese medicine (TCM) plays an important role in the prevention and treatment of COPD. AIM OF THE STUDY: The objective of this review is to summarize the TCM theories, experimental methods, TCM extracts, active TCM ingredients, and TCM formulas for the treatment of COPD and reveal the effects and mechanisms of TCM treatments on COPD. MATERIALS AND METHODS: This article reviewed literature on TCM-based treatments for COPD reported from 2016 to 2021. Relevant scientific studies were obtained from databases that included PubMed, China National Knowledge Infrastructure, Web of Science, Google Scholar, The Plant List, ScienceDirect, and SciFinder. RESULTS: This review summarized TCM-based theory, experimental methods, active ingredients, and potential toxicities, the effects of TCM extracts and formulations, and their mechanisms for the treatment of COPD. Most investigators have used in vivo models of cigarette smoke combined with lipopolysaccharide induction in rats and in vitro models of cigarette smoke extract induction. The active ingredients of TCM used for the treatment of COPD in relevant studies were triterpenoids, flavonoids, phenolics, quinones, glycosides, and alkaloids. TCMs commonly used in the treatment of COPD include antipyretic drugs, tonic medicines, anticough medications, and asthma medications. TCM can treat COPD by suppressing inflammation, reducing oxidative stress, inhibiting apoptosis, and improving airway remodeling. CONCLUSIONS: This review enriches the theory of COPD treatments based on TCM, established the clinical significance and development prospects of TCM-based COPD treatments, and provided the necessary theoretical support for the further development of TCM resources for the treatment of COPD.

Structural characterization and anti-inflammatory effects of an arabinan isolated from Rehmannia glutinosa Libosch.

Considering that natural polysaccharides are potential anti-inflammatory agents, in this study, an arabinan (RGP70-2) was isolated and purified from Rehmannia glutinosa Libosch. (R. glutinosa) and its structure was characterized. RGP70-2 was a homogeneous polysaccharide with a molecular weight of 6.7 kDa, with the main backbone comprising →5)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →2,3,5)-α-L-Araf-(1→, and →2,5)-α-L-Araf-(1 â†’ linkages and the side chain comprising an α-L-Araf-(1 â†’ linkage. In vivo experiments showed that RGP70-2 inhibited ROS production and downregulated the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). In vitro experiments showed that RGP70-2 decreased levels of pro-inflammatory cytokines, inhibited ROS production, and attenuated NF-κB-p65 translocation from the cytoplasm to the nucleus. Our results showed that RGP70-2 may delay inflammation by regulating the ROS-NF-κB pathway. Thus, RGP70-2 has potential applications as an anti-inflammatory agent in the biopharmaceutical industry.

Inhibition of inflammasome activation via sphingolipid pathway in acute lung injury by Huanglian Jiedu decoction: An integrative pharmacology approach.

BACKGROUND: Acute lung injury (ALI) is a serious health issue which causes significant morbidity and mortality. Inflammation is an important factor in the pathogenesis of ALI. Even though ALI has been successfully managed using a traditiomal Chinese medicine (TCM), Huanglian Jiedu Decoction (HLD), its mechanism of action remains unknown. PURPOSE: This study explored the therapeutic potential of HLD in lipopolysaccharide (LPS)-induced ALI rats by utilizing integrative pharmacology. METHODS: Here, the therapeutic efficacy of HLD was evaluated using lung wet/dry weight ratio (W/D), myeloperoxide (MPO) activity, and levels of tumor necrosis factor (TNF-α), interleukin (IL)-1ß and IL-6. Network pharmacology predictd the active components of HLD in ALI. Lung tissues were subjected to perform Hematoxylin-eosin (H&E) staining, metabolomics, and transcriptomics. The acid ceramidase (ASAH1) inhibitor, carmofur, was employedto suppress the sphingolipid signaling pathway. RESULTS: HLD reduced pulmonary edema and vascular permeability, and suppressed the levels of TNF-α, IL-6, and IL-1ß in lung tissue, Bronchoalveolar lavage fluid (BALF), and serum. Network pharmacology combined with transcriptomics and metabolomics showed that sphingolipid signaling was the main regulatory pathway for HLD to ameliorate ALI, as confirmed by immunohistochemical analysis. Then, we reverse verified that the sphingolipid signaling pathway was the main pathway involed in ALI. Finally, berberine, baicalein, obacunone, and geniposide were docked with acid ceramidase to further explore the mechanisms of interaction between the compound and protein. CONCLUSION: HLD does have a better therapeutic effect on ALI, and its molecular mechanism is better elucidated from the whole, which is to balance lipid metabolism, energy metabolism and amino acid metabolism, and inhibit NLRP3 inflammasome activation by regulating the sphingolipid pathway. Therefore, HLD and its active components can be used to develop new therapies for ALI and provide a new model for exploring complex TCM systems for treating ALI.

Traditional Chinese medicines as effective agents against influenza virus-induced pneumonia.

Influenza virus-induced pneumonia (IVP) is a high morbidity and contagiousness pulmonary infectious disease caused by invasion of the influenza virus into the lower respiratory tract. Currently, the treatment of IVP is mainly based on an anti-influenza virus infection strategy, which includes the use of anti-influenza vaccines and drugs. However, the clinical use of these treatment options is limited as the influenza virus has a high level of variability and drug resistance may occur. Traditional Chinese medicines (TCMs) for the treatment of IVP have unique advantages, a variety of precise curative effects and have been widely used in clinical practice in China both historically and in the present day. However, there are only few literature reviews on the prevention and treatment of IVP using TCMs. Therefore, we conducted a review of relevant literature from the past 10 years and a comprehensive analysis of various databases containing reports on TCMs used for IVP prevention and treatment to provide basic data for future research and development of drugs against IVP. Herein, we summarize research progress on the pathogenesis of IVP, the TCMs effective in prevention or treatment of IVP, their underlying molecular mechanisms and active components. Overall, we provide a theoretical basis for the clinical use of TCM in the prevention and treatment of IVP. Furthermore, we provide a reference for the development of new multi-component, multi-target, low-toxicity drugs, which is of great academic and clinical significance.

Physalis alkekengi L. var. franchetii (Mast.) Makino: A review of the pharmacognosy, chemical constituents, pharmacological effects, quality control, and applications.

BACKGROUND: Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) (Chinese name Jin-Deng-Long) from the Solanaceae family is a traditional Chinese medicine with various pharmacological effects, such as removing heat, detoxification, improving throat conditions, removing phlegm, and ameliorating diuresis. PURPOSE: This paper reviews the existing literature and patents and puts forward some suggestions for future PAF research. METHODS: Using the PubMed, Google Scholar, Web of Science, and China National Knowledge Infrastructure databases, we performed comprehensive search of literature and patents published before April 2022 on PAF and its active ingredients. RESULTS: We comprehensively reviewed the research progress of PAF from aspects of the traditional application, botany, chemical composition, pharmacological effects, and toxicology, and first discussed quality control and modern applications, which have not been explored in previous reviews. Thereafter, we reviewed the limitations of pharmacological mechanism and quality control studies and proposed appropriate solutions, which is of great practical significance to subsequent studies. CONCLUSION: In this review, we present a comprehensive overview on PAF, and put forward new insights on studies regarding quality control, material basis, and mechanisms in classical prescription, providing theoretical guidance for the clinical application and development of Chinese medicine.

Integrative pharmacology reveals the mechanisms of Erzhi Pill, a traditional Chinese formulation, against diabetic cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Erzhi Pill (EZP) is a traditional Chinese prescription that has marked effects in treating type 2 diabetes mellitus and diabetic nephropathy. However, its underlying pharmacological mechanisms in the treatment of diabetic cardiomyopathy (DCM), remain to be elucidated. AIM OF THE STUDY: This study aimed to apply an integrative pharmacological strategy to systematically evaluate the pharmacological effects and molecular mechanisms of EZP, and provide a solid theoretical basis for the clinical application of EZP in the treatment of DCM. MATERIALS AND METHODS: In this study, the potential targets and key pathways of EZP were predicted and validated using network pharmacology and molecular docking, respectively. Changes in cardiac metabolites and major metabolic pathways in rat heart samples were examined using 1H-nuclear magnetic resonance (NMR) metabolomics. Finally, biochemical analysis was conducted to detect the protein expression levels of key pathways. RESULTS: We found that EZP decreased fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels, increased high-density lipoprotein (HDL) levels in the serum, and alleviated the morphological abnormalities of the heart tissue in diabetic rats. Furthermore, EZP effectively restored superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspase-3, caspase-8, and caspase-9 activity levels, as well as the levels of reactive oxygen species (ROS), malondialdehyde (MDA), B-cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax) in the heart tissue. Network pharmacology prediction results indicated that the mechanism of EZP in treating DCM was closely related to apoptosis, oxidative stress, and the HIF-1, PI3K-Akt, and FoxO signaling pathways. In addition, 1H-NMR metabolomics confirmed that EZP primarily regulated both energy metabolism and amino acid metabolism, including the tricarboxylic acid (TCA) cycle, ketone bodies metabolism, glutamine and glutamate metabolism, glycine metabolism, and purine metabolism. Finally, immunohistochemistry results indicated that EZP reduced the expression levels of p-AMPK, p-PI3K, p-Akt, and p-FoxO3a proteins, in the heart tissue of DCM rats. CONCLUSION: The results confirmed that the overall therapeutic effect of EZP in the DCM rat model is exerted via inhibition of oxidative stress and apoptosis, alongside the regulation of energy metabolism and amino acid metabolism, as well as the AMPK and PI3K/Akt/FoxO3a signaling pathways. This study provides an experimental basis for the use of EZP in DCM treatment.

Integrated Pharmacology Reveals the Molecular Mechanism of Gegen Qinlian Decoction Against Lipopolysaccharide-induced Acute Lung Injury.

ALI is a severe inflammatory disease of the lungs. In previous studies, we found that GQD was effective against ALI, but specific molecular mechanism is still unclear. Therefore, this study was to examine effect of GQD on LPS-induced ALI rats and underlying mechanisms using multi-omics and molecular methods. The results showed that GQD significantly improved lung tissue damage, reduced pulmonary edema, inhibited MPO activity, and improved respiratory function in ALI rat. Additionally, GQD significantly reduced the levels of TNF-α, IL-1ß, and IL-6 in serum and BALF. Furthermore, metabolomic analysis showed that GQD reduced pulmonary inflammation by improving metabolic remodeling. Moreover, transcriptomic analysis showed that GQD inhibited the activation of complement pathway and regulated Th17 and Treg cells balance. Additionally, GQD inhibited the expression of C3, C5a, and IL-17, and promoted the expression of TGF-ß and CYP1A1 at the mRNA and protein levels. Gut microbial assay showed that GQD treatment increased the relative abundance of Firmicutes and their genera in intestinal microbiota, and increased short-chain fatty acids concentration. Overall, GQD treated ALI by improving metabolic remodeling, affecting immune-related pathways and regulating intestinal microbiota. This study provides a solid scientific basis for promoting the clinical use of GQD in treating ALI.