The Landscape of Gut Microbiota and Its Metabolites: A Key to Understanding the Pathophysiology of Pattern in Chinese Medicine.

Liver Stagnation and Spleen Deficiency (LSSD) is a Chinese Medicine (CM) pattern commonly observed in gastrointestinal (GI) diseases, yet its biological nature remains unknown. This limits the global use of CM medications for treating GI diseases. Recent studies emphasize the role of gut microbiota and their metabolites in the pathogenesis and treatment of LSSD-associated GI diseases. There is increasing evidence supporting that an altered gut microbiome in LSSD patients or animals contributes to GI and extra-intestinal symptoms and affects the effectiveness of CM therapies. The gut microbiota is considered to be an essential component of the biological basis of LSSD. This study aims to provide an overview of existing research findings and gaps for the pathophysiological study of LSSD from the gut microbiota perspective in order to understand the relationship between the CM pattern and disease progression and to optimize CM-based diagnosis, prevention, and therapy.

Aqueous cinnamon extract ameliorates bowel dysfunction and enteric 5-HT synthesis in IBS rats.

Cinnamon protects against irritable bowel syndrome with diarrhea (IBS-D) in humans, but its efficacy and underlying mechanism of action remain poorly understood. Maternally separated (MS) IBS-D rat model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced post-inflammatory IBS-D rat model are characterized by visceral hyperalgesia and diarrhea. This study used the two models to evaluate the effect of cinnamon extract (CE) on bowel symptoms. The MS rat model was also used to explore its underlying anti-IBS mechanism. cinnamon extract reduced defecation frequency and visceral hyperalgesia in MS rats in a dose-dependent manner and effectively improved visceral hyperalgesia in TNBS rats. The efficacy of cinnamon extract was comparable to the positive drug serotonin receptor 3 (5-HT3) selective antagonist, Ramosetron. Excessive 5-HT, a well-known pathogenic factor for IBS, in the colon and circulation of IBS rats was reduced after cinnamon extract intervention. Both, gene and protein levels of the colonic 5-HT synthetase, Tryptophan Hydroxylase 1 (Tph1), were also decreased in CE-treated IBS rats. In addition, a luciferase assay revealed that cinnamon extract and its major components, catechin, procyanidin B1/2, cinnamic acid, and cinnamyl alcohol, significantly inhibited Tph1 transcription activity in vitro. These findings illustrated that aqueous cinnamon extract partially attenuated bowel symptoms in IBS models by directly inhibiting Tph1 expression and controlling 5-HT synthesis. This provides a scientific viewpoint for the use of cinnamon as a folk medication to treat IBS.

Moxibustion Exerts a Neuroprotective Effect through Antiferroptosis in Parkinson's Disease.

The objective of this study was to explore the neuroprotective effect of moxibustion on rats with Parkinson's disease (PD) and its mechanism. A Parkinson's disease model was established in rats using a two-point stereotactic 6-hydroxydopamine injection in the right substantia nigra (SN) and ventral tegmental area. The rats received moxibustion at the Baihui (GV20) and Sishencong (EX-HN1) acupoints for 20 minutes, six times a week, for 6 weeks. The right SN tissue was histologically and immunohistochemically examined. Differentially expressed genes (DEGs) were identified through RNA sequencing. In addition, the levels of tyrosine hydroxylase (TH), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) in SN were measured. In comparison to the model group, the moxibustion group showed a significantly greater TH immunoreactivity and a higher behavioural score. In particular, moxibustion led to an increase in the number and morphological stability of SN neural cells. The functional pathway analysis showed that DEGs are closely related to the ferroptosis pathway. GPX4 and FTH1 in the SN were significantly overexpressed in the moxibustion-treated rats with PD. Moxibustion can effectively reduce the death of SN neurons, decrease the occurrence of ferroptosis, and increase the TH activity to protect the neurons in rats with PD. The protective mechanism may be associated with suppression of the ferroptosis.

Steric Effect of Antioxidant Diels-Alder-Type Adducts: A Comparison of Sanggenon C with Sanggenon D.

Sanggenons C and D are two Diels-Alder-type adducts from Chinese crude drug Sang-bai-pi. Structurally, both sanggenons construct stereoisomers. In the study, they were comparatively determined using four antioxidant assays, including ferric ion reducing antioxidant power (FRAP) assay, Cu2+-reducing assay, 1,1-diphenyl-2-picryl-hydrazl (DPPH•)-scavenging assay, and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid radical (ABTS•⁺)-scavenging assay. Their Fe2+-binding reactions were explored using UV-Vis spectra. Finally, their cytoprotective effects were evaluated using flow cytometry. In electron transfer (ET)-based FRAP and Cu2+-reducing assays, sanggenon D was found to have lower IC50 values than sanggenon C; however, in multi-pathway-based DPPH•-scavenging and ABTS•⁺-scavenging assays, sanggenon C possessed lower IC50 values than sanggenon D. UV-Vis spectra suggested that sanggenon C generated a bathochromic-shift (286 nm → 302 nm) and displayed stronger UV absorption than sanggenon D. In flow cytometry, sanggenon C and sanggenon D, respectively, exhibited 31.1% and 42.0% early apoptosis-percentages towards oxidative-stressed mesenchymal stem cells (MSCs). In conclusion, both sanggenons may undergo multiple pathways (e.g., ET and Fe2+-binding) to protect MSCs against oxidative stress. In the mere ET aspect, sanggenon D possesses a higher level than sanggenon C, while in multi-pathway-based radical-scavenging, Fe2+-binding, and cytoprotection aspects, sanggenon C is more active than sanggenon D. These discrepancies can conclusively be attributed to the steric effect.

Antioxidant and Cytoprotective Effects of Tibetan Tea and Its Phenolic Components.

Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea (LATT) was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic acid, and four catechins (i.e., (+)-catechin, (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate). Gallic acid, the four catechins, and LATT were then comparatively investigated by four antioxidant assays: ferric reducing antioxidant power, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) scavenging, 1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging assays. In these assays, LATT, along with the five phenolic components, increased their antioxidant effects in a concentration-dependent manner; however, the half maximal scavenging concentrations of ECG were always lower than those of CG. Gallic acid and the four catechins were also suggested to chelate Fe2+ based on UV-visible spectral analysis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis suggested that, when mixed with PTIO•, the five phenolic components could yield two types of radical adduct formation (RAF) products (i.e., tea phenolic dimers and tea phenolic-PTIO• adducts). In a flow cytometry assay, (+)-catechin and LATT was observed to have a cytoprotective effect towards oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this evidence, we concluded that LATT possesses antioxidative or cytoprotective properties. These effects may mainly be attributed to the presence of phenolic components, including gallic acid and the four catechins. These phenolic components may undergo electron transfer, H⁺-transfer, and Fe2+-chelating pathways to exhibit antioxidative or cytoprotective effects. In these effects, two diastereoisomeric CG and ECG showed differences to which a steric effect from the 2-carbon may contribute. Phenolic component decay may cause RAF in the antioxidant process.