Benzoylmesaconine mitigates NLRP3 inflammasome-related diseases by reducing intracellular K efflux and disrupting NLRP3 inflammasome assembly.

Background: Benzoylmesaconine (BMA), a major alkaloid derived from the traditional Chinese medicine Aconitum carmichaeli Debx, exhibits potent anti-inflammatory properties. However, the precise mechanism underlying its action remains unclear.

Purpose: This study aimed to investigate the inhibitory mechanism of BMA on the NLRP3 inflammasome and assess its therapeutic efficacy in NLRP3-related metabolic diseases.

Palbociclib-derived multifunctional molecules for lysosomal targeting and diagnostic-therapeutic integration.

Lysosomal pH changes are associated with drug resistance, cell growth and invasion of tumors, but effective and specific real-time monitoring of lysosomal pH compounds for cancer therapy is lacking. Here, based on the covalent linkage of the anticancer drug palbociclib and fluorescent dye fluorescein isothiocyanate (FITC), we designed and developed a novel palbociclib-derived multifunctional molecule (Pal-FITC) for lysosomal targeting and diagnostic therapeutic integration. Pal-FITC fluoresces is 20-fold stronger than that of FITC and shows a linear response in the pH range of 4.

Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.

Piper longum L. ameliorates gout through the MAPK/PI3K-AKT pathway.

Ethnopharmacological Relevance: Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade.

Comparison of the efficacy and safety of benzbromarone and febuxostat in gout and hyperuricemia: a systematic review and meta-analysis.

Objective: Urate-lowering therapy (ULT) is widely recognized as the primary treatment for hyperuricemia and gout. Xanthine oxidase inhibitors (XOI), particularly febuxostat, have gained popularity as a frontline approach. However, the divergent efficacy and safety between febuxostat and the traditional ULT drug, benzbromarone, remain poorly understood.

Oral delivery of porous starch-loaded bilayer microgels for controlled drug delivery and treatment of ulcerative colitis.

We prepared one type of bilayer microgels for oral administration with three effects: pH responsiveness, time lag, and colon enzyme degradation. Combined with the dual biological effects of curcumin (Cur) for reducing inflammation and promoting repair of colonic mucosal injury, targeted colonic localization and release of Cur according to the colonic microenvironment were enhanced. The inner core, derived from guar gum and low-methoxyl pectin, afforded colonic adhesion and degradation behavior; the outer layer, modified by alginate and chitosan via polyelectrolyte interaction, achieved colonic localization.

The immunosuppressive effects and mechanisms of loureirin B on collagen-induced arthritis in rats.

Introduction: Rheumatoid arthritis (RA) is a common disease mainly affecting joints of the hands and wrists. The discovery of autoantibodies in the serum of patients revealed that RA belonged to the autoimmune diseases and laid a theoretical basis for its immunosuppressive therapy. The pathogenesis of autoimmune diseases mainly involves abnormal activation and proliferation of effector memory T cells, which is closely related to the elevated expression of Kv1.

Effects of Shiwei Longdanhua formula on LPS induced airway mucus hypersecretion, cough hypersensitivity, oxidative stress and pulmonary inflammation.

Shiwei Longdanhua Granule (SWLDH) is a classic Tibetan medicine (TM) ranking in the top 20 Chinese patent medicines in prescription rate to treat respiratory diseases like pneumonia, acute and chronic tracheobronchitis, acute exacerbation of COPD and bronchial asthma in solution of inflammation, cough and phlegm obstruction in clinical practice. However, its systematic pharmacological mechanisms have not been elucidated yet. Here, we studied the therapeutic efficacy of SWLDH in treatment of acute respiratory diseases in BALB/c mice by comprehensive analysis of airway inflammation, oxidative stress, mucus hypersecretion, cough hypersensitivities and indicators associated with the development of chronic diseases.

Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma ameliorate scopolamine-induced cognitive impairment by regulating the cholinergic and synaptic associated proteins.

Ethnopharmacological Relevance: The combination of Polygoni Multiflori Radix Praeparata (PMRP) and Acori Tatarinowii Rhizoma (ATR) is often used in traditional Chinese medicine to prevent and treat Alzheimer's disease (AD). However, it is not clear whether the effects and mechanisms of the decoction prepared by traditional decocting method (PA) is different from that prepared by modern decocting method (P + A).

Aim Of The Study: The present study aimed to investigate the differences in the protective effects of PA and P + A on scopolamine induced cognitive impairment, and to explore its potential mechanism.

A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain.

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood.

Potential anti-gout properties of Wuwei Shexiang pills based on network pharmacology and pharmacological verification.

Ethnopharmacological Relevance: Wuwei Shexiang Pills (WWSX), a classic Tibetan medicine, consists of Chebulae Fructus (removed pit), Aucklandiae Radix, Moschus, Aconiti Fiavi Radix, and Acori Calami Rhizoma. It is used clinically in China to treat joint pain, swelling and other symptoms, and has the function of dispelling wind and relieving pain. However, to date, the mechanism of how it works against gout is still unclear.

Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity.

Inflammatory and functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and obstructive bowel disorder (OBD) underlie the most prevalent forms of visceral pain. Although visceral pain can be generally provoked by mechanical distension/stretch, the mechanisms that underlie visceral mechanosensitivity in colon-innervating visceral afferents remain elusive. Here, we show that virally mediated ablation of colon-innervating TRPV1-expressing nociceptors markedly reduces colorectal distention (CRD)-evoked visceromotor response (VMR) in mice.

Chemotherapy-induced phlebitis via the GBP5/NLRP3 inflammasome axis and the therapeutic effect of aescin.

Background And Purpose: Intravenous infusion of chemotherapy drugs can cause severe chemotherapy-induced phlebitis (CIP) in patients. However, the underlying mechanism of CIP development remains unclear.

Experimental Approach: RNA-sequencing analysis was used to identify potential disease targets in CIP.

Integrating network pharmacology and pharmacological validation to explore the effect of Shi Wei Ru Xiang powder on suppressing hyperuricemia.

Ethnopharmacological Relevance: Shi Wei Ru Xiang powder (SWR) is a traditional Tibetan medicinal formula with the effect of dispelling dampness and dispersing cold. In clinical practice, SWR is generally used for the treatment of hyperuricemia (HUA). However, its exact pharmacological mechanism remains unclear.

Epimedii Folium and Curculiginis Rhizoma ameliorate lipopolysaccharides-induced cognitive impairment by regulating the TREM2 signaling pathway.

Ethnopharmacological Relevance: Neuroinflammation induced by microglia is closely related to a variety of neurodegenerative diseases including Alzheimer's disease (AD). Previous study has found that aqueous extract of Epimedii Folium and Curculiginis Rhizoma (EX) had anti-inflammatory effect on AD by activating the NLRP3 inflammasome and inhibiting NF-κB/MAPK pathway. However, whether the anti-neuroinflammatory effect of EX is related to microglia or not remains unclear.

Mechanosensitive TRPV4 is required for crystal-induced inflammation.

Crystal structures activate innate immune cells, especially macrophages and initiate inflammatory responses. We aimed to understand the role of the mechanosensitive TRPV4 channel in crystal-induced inflammation. Real-time RT-PCR, RNAscope in situ hybridisation, and mice were used to examine TRPV4 expression and whole-cell patch-clamp recording and live-cell Ca imaging were used to study TRPV4 function in mouse synovial macrophages and human peripheral blood mononuclear cells (PBMCs).

Combination of Polygoni Multiflori Radix Praeparata and Acori Tatarinowii Rhizoma Alleviates Learning and Memory Impairment in Scopolamine-Treated Mice by Regulating Synaptic-Related Proteins.

Polygoni Multiflori Radix Praeparata (ZhiHeShouWu, PMRP) and Acori Tatarinowii Rhizoma (ShiChangPu, ATR) and their traditional combination (PA) are frequently used in traditional Chinese medicine to prevent and treat Alzheimer disease (AD) based on the theory that PMRP tonifies the kidney and ATR dissipates phlegm. However, the components of PA and their mechanisms of action are not known. The present study analyzed the active components of PA, and investigated the protective effect of PA against cognitive impairment induced by scopolamine in mice along with the underlying mechanism.

Hepatoprotection of Herpetospermum caudigerum Wall. against CCl-induced liver fibrosis on rats.

Ethnopharmacological Relevance: Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk.

Aim Of The Study: Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end.

Hepatoprotective effect of Herpetospermum caudigerum Wall. on carbon tetrachloride-induced hepatic fibrosis in rats.

Tibetan medicine Herpetospermum caudigerum Wall. (HCW) has long been employed to treat hepatitis, inflammatory diseases and jaundice according to the records of "The Four Medical Tantras" in China. This study was investigated to explore the protective effects of HCW on hepatic fibrosis and the possible mechanism in a rat model.

Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway.

The current study was designed to investigate the hepatoprotective effects and possible mechanisms of Baicalein (BA) on the diabetic liver injury in vivo and in vitro. The results exhibited that BA significantly restored the blood glucose in oral glucose tolerance test (OGTT) and inhibited the levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) in C57BL/KsJ-db/db mice. Moreover, BA strikingly attenuated the extent of steatosis in the liver tissues of diabetic mice.

Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway.

Ethnopharmacological Relevance: Entada phaseoloides (L.) Merr., a traditional Chinese folk medicine, has been used in treating diabetes and other inflammatory disorders.

Salidroside suppressing LPS-induced myocardial injury by inhibiting ROS-mediated PI3K/Akt/mTOR pathway in vitro and in vivo.

The purpose of the present study was to investigate the effect of salidroside (Sal) on myocardial injury in lipopolysaccharide (LPS)-induced endotoxemic in vitro and in vivo. SD rats were randomly divided into five groups: control group, LPS group (15 mg/kg), LPS plus dexamethasone (2 mg/kg), LPS plus Sal groups with different Sal doses (20, 40 mg/kg). Hemodynamic measurement and haematoxylin and eosin staining were performed.

The protective effect of Epimedii Folium and Curculiginis Rhizoma on Alzheimer's disease by the inhibitions of NF-κB/MAPK pathway and NLRP3 inflammasome.

The purpose of the current study was to explore the effects of the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX) on Aβ-induced Alzheimer's disease. Aβ1-42 was stereotaxically injected bilaterally into the dorsal hippocampus, and then the rats were orally received EX at the doses of 2 g/kg and 6 g/kg for 30 days. Behavior was monitored through Morris water maze test.