[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

[Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization].

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

Objective: The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS). Methods: A comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk. Results: A total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54, p = 0.009, seven studies), FBS (MD = -8.6, 95% CI: -15.45 to -1.75, p = 0.01, nine studies), DBP (MD = -2.8, 95% CI: -4.53 to - 1.06, p = 0.002, five studies), HDL-C (MD = 4.98, 95% CI: 2.58 to 7.38, p < 0.0001, eight studies), TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, p < 0.00001, two studies), CRP (MD = - 1.24, 95% CI: -1.71 to -0.77, p < 0.00001, two studies), and MDA (MD = -2.35, 95% CI: -4.47 to -0.24, p = 0.03, three studies). These improvements were statistically significant. Meanwhile, there was no significant improvement in SBP (MD = -4.82, 95% CI: -9.98 to 0.35, p = 0.07, six studies), TG (MD = 1.28, 95% CI: -3.75 to 6.30, p = 0.62, eight studies), IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, p = 0.23, two studies), or hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, p < 0.51, two studies). FBS, SBP, HDL-C, IL-6, CRP, hsCRP, and MDA had a relatively high heterogeneity. Conclusion: Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022362553.

[Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy].

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Natural and Pseudonatural Lindenane Heterodimers from Sarcandra glabra by Molecular Networking.

Sarglaoxolane A (1), the first lindenane-normonoterpene heterodimer fused by tetrahydrofuran, was discovered in Sarcandra glabra guided by the first proposed single-node-based molecular networking approach. Moreover, two pseudonatural derivatives (2 and 3) with an oxa-difuranofurone moiety were transformed from 1 and confirmed by X-ray diffraction, and also proven to exist in the plant extract. A combination of molecular networking and biomimetic transformation can significantly promote the discovery and structural elucidation of novel natural products.

3,4-Seco-Isopimarane Diterpenes from the Twigs and Leaves of Isodon Flavidus.

Three isopimarane diterpenes [fladins B (1), C (2), and D (3)] were isolated from the twigs and leaves of Chinese folk medicine, Isodon flavidus. The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of 1-3 were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new δ-lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of 1, molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the b axis. Compounds 1-3 were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against Trichophyton rubrum and T. mentagrophytes, or antiviral activities against HIV entry at 20 µg/mL (62.9-66.7) µM. Compounds 1 and 3 did not show antiviral activities against Ebola entry at 20 µg/mL either; only 2 was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.

Automatic MS/MS Data Mining Strategy for Discovering Target Natural Products: A Case of Lindenane Sesquiterpenoids.

Untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a widely used method for discovering natural products (NPs); however, automatic MS/MS data mining for the discovery of NPs remains a challenge. In this work, LindenaneExtractor, a program based on characteristic MS/MS ions of lindenane sesquiterpenoids (LSs) was developed to automatically extract the LSs features for target LS discovery in plant extracts. To build this program, fragmentation mechanisms of characteristic ions of LSs were elucidated and confirmed by quantum chemical calculation and deuterium-labeled compounds. Subsequently, the information of characteristic ions was integrated and coded to develop LindenaneExtractor, which was further examined by standards and several public databases. Finally, the target LS features in Sarcandra hainanensis extract were automatically extracted by LindenaneExtractor and visualized by feature-based molecular networking and two-dimensional (2D) retention time-m/z plot, leading to the discovery of 96 target LSs in total, 37 of these compounds were potentially new NPs and one was confirmed by further isolation. This work proposed a new strategy for target NP analysis and discovery based on automatic MS/MS data mining, which could significantly improve the efficiency and accuracy of NP discovery.

Sesquiterpenoids from the leaves of Sarcandra glabra.

Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 µmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.

The anti-inflammatory activity by suppressing the TRAF6/MAPKs pathway of trishizukaol a from Sarcandra glabra.

BACKGROUND: Sarcandra glabra (Thunb.) Makino (Chloranthaceae) is abundant and shows important clinical effects. Traditionally, S.glabra is used to treat diseases involving inflammation, such as bone fracture and joint swelling. Lindenane-type sesquiterpenoids and dimers are the major anti-inflammatory components in S. glabra. Trishizukaol A (TSA), is an abundant lindenane sesquiterpenoid trimer in S.glabra, but its anti-inflammatory activities and mechanisms are poorly understood. PURPOSE: The study was undertaken to unveil the inhibition of inflammation and mechanism of TSA in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). METHODS: Griess reagent and ELISA were utilized to measure nitric oxide (NO) production and inflammatory cytokines, respectively. Signal proteins such as JNK, nuclear factor E2-related factor 2 (Nrf2) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were quantitatively evaluated in western blot experiments. Flow cytometry was used to determine the concentration of reactive oxygen species (ROS). More importantly, Drug Affinity Responsive Target Stability (DARTS) assay and molecular docking were conducted to investigate the potential targets of TSA. RESULTS: TSA effectively reduced the NO production (half-maximal inhibitory concentration (IC50) at 12.53 ± 0.31 µM). In addition, TSA restrained the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and it could up-regulate the levels of interleukin-10 (IL-10). TSA also decreased ROS levels by enhancing the levels of Nrf2 protein and its related target genes. Meanwhile, TSA regulated the nuclear translocation of nuclear factor-κB (NF-κB) by suppressing the MAPKs signaling pathway. Importantly, TSA may suppress the inflammation through the TRAF6/MAPKs pathway. CONCLUSION: TSA suppressed the inflammatory mechanism mediated by the TRAF6/MAPKs pathway. Our research first revealed the anti-inflammatory effect of a lindenane sesquiterpenoid trimer, providing a therapeutic drug candidate for inflammatory diseases. Furthermore, the lindenane-type sesquiterpenoid trimers may be among the main anti-inflammatory components in S. glabra.

Integrated molecular networking strategy enhance the accuracy and visualization of components identification: A case study of Ginkgo biloba leaf extract.

Molecular networking (MN) is an efficient tool for natural product research. However, single MN might lead to false annotation due to the limited information, and the importance of combining MN with chromatogram is always ignored. In this study, we proposed a comprehensive MN strategy combining feature-based molecular networking (FBMN) and dual ionization mode MS/MS to improve the annotation accuracy and to achieve structural feature visualization in a chemotaxonomic chromatogram. Three steps were taken: (1) employing FBMN and dual ionization mode MS/MS to distinguish isomers and improve components' identification accuracy. (2) Using a 3-level initiative supported by in-house database to evaluate the annotation confidence. As a result, 95 compounds were successfully identified from Ginkgo biloba leaf extract (GBE) and Ginkgo biloba leaf (GBL), and 70 compounds mainly consisting of flavonoid glycosides, ginkgolides, and lignan glycosides were assigned as high-confidence molecules. (3) Building color-dependent chemotaxonomic chromatograms, to achieve component visualization by connecting FBMN with chromatogram in which the peaks of the same color indicated the compounds with similar structural features. Our research provided a new and efficient strategy for component identification and visualization of herbal medicine.

Calcium chloride and 1-methylcyclopropene treatments delay postharvest and reduce decay of New Queen melon.

In this study, newly harvested New Queen melons were treated with calcium chloride (CaCl2) and 1-methylcyclopropene (1-MCP) alone or in combination before storage. The results showed that the respiration rate, ethylene release, the activity and gene expression of pectinases such as polygalacturonase (PG), pectin methylesterase (PME) and pectate lyase (PL) in New Queen melons were dramatically decreased by treatments with 0.18 mol/L CaCl2 and/or 1 µL/L 1-MCP. Meanwhile, the climacteric behavior and flesh hardness reduction were inhibited. We also found that softer melon flesh was more conducive to the growth and reproduction of decay-causing microorganisms according to their growth curves in melons that were different in flesh hardness, suggesting inhibiting fruit softening can slow down the growth of microorganisms in fruit flesh, and thus reduce fruit decay rate. The combined use of CaCl2 and 1-MCP was more effective in suppressing respiration rate, ethylene release and protopectin hydrolysis, which could greatly delay the softening, reduce the decay rate, and extend the shelf life of New Queen melons.

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

ETHNOPHARMACOLOGICAL RELEVANCE: Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. AIM OF THE STUDY: The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. MATERIALS AND METHODS: The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. RESULTS: Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8µg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5µg/mL. CONCLUSIONS: Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.

Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2).

Sesquiterpenes and other constituents from Achillea wilsoniana.

From the methanol extract of the whole plant of Achillea wilsoniana, 23 compounds were isolated. Their structures were elucidated by spectroscopic methods and chemical transformations. Three of them are new: 4E, 10E-9beta-hydroxy-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6alpha-olide (1), 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6alpha-olide (2) and 1beta,6a-dihydroxy-10beta-methyl-5alphaH,7alphaH-eudesm-4-one (3). In addition, 1beta-hydroxy-alpha-xyperone (5) and 9beta-acetoxy-3-(2methylbutyroyloxy)-germacra-4,10(1)-diene-12,6alpha-olide (1a) exhibited effective antibacterial activity against Staphylococcus aureus.