Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn's disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.

The mechanism of traditional medicine in alleviating ulcerative colitis: regulating intestinal barrier function.

Ulcerative colitis (UC) is an idiopathic inflammatory disease mainly affects the large bowel and the rectum. The pathogenesis of this disease has not been fully elucidated, while the disruption of the intestinal barrier function triggered by various stimulating factors related to the host genetics, immunity, gut microbiota, and environment has been considered to be major mechanisms that affect the development of UC. Given the limited effective therapies, the treatment of this disease is not ideal and its incidence and prevalence are increasing. Therefore, developing new therapies with high efficiency and efficacy is important for treating UC. Many recent studies disclosed that numerous herbal decoctions and natural compounds derived from traditional herbal medicine showed promising therapeutic activities in animal models of colitis and have gained increasing attention from scientists in the study of UC. Some of these decoctions and compounds can effectively alleviate colonic inflammation and relieve clinical symptoms in animal models of colitis via regulating intestinal barrier function. While no study is available to review the underlying mechanisms of these potential therapies in regulating the integrity and function of the intestinal barrier. This review aims to summarize the effects of various herbal decoctions or bioactive compounds on the severity of colonic inflammation via various mechanisms, mainly including regulating the production of tight junction proteins, mucins, the composition of gut microbiota and microbial-associated metabolites, the infiltration of inflammatory cells and mediators, and the oxidative stress in the gut. On this basis, we discussed the related regulators and the affected signaling pathways of the mentioned traditional medicine in modulating the disruption or restoration of the intestinal barrier, such as NF-κB/MAPK, PI3K, and HIF-1α signaling pathways. In addition, the possible limitations of current studies and a prospect for future investigation and development of new UC therapies are provided based on our knowledge and current understanding. This review may improve our understanding of the current progression in studies of traditional medicine-derived therapies in protecting the intestinal barrier function and their roles in alleviating animal models of UC. It may be beneficial to the work of researchers in both basic and translational studies of UC.

Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential.

Inflammatory bowel disease (IBD), mainly including Crohn's disease and ulcerative colitis, seriously affects human health and causes substantial social and economic burden. The pathogenesis of IBD is still not fully elucidated, whereas recent studies have demonstrated that its development is associated with the dysfunction of intestinal immune system. Accumulating evidence have proven that inflammasomes such as NLRP3 and NLRP6 play a prominent role in the pathogenesis of IBD. Thus, regulating the activation of inflammasomes have been considered to be a promising strategy in IBD treatment. A number of recent studies have provided evidence that blocking inflammasome related cytokine IL-1ß can benefit a group of IBD patients with overactivation of NLRP3 inflammasome. However, therapies for targeting inflammasomes with high efficacy and safety are rare. Traditional medical practice provides numerous medical compounds that may have a role in treatment of various human diseases including IBD. Recent studies demonstrated that numerous medicinal herb derived compounds can efficiently prevent colon inflammation in animal models by targeting inflammasomes. Herein, we summarize the main findings of these studies focusing on the effects of traditional medicine derived compounds on colitis treatment and the underlying mechanisms in regulating the inflammasomes. On this basis, we provide a perspective for future studies regarding strategies to improve the efficacy, specificity and safety of available herbal compounds, and to discover new compounds using the emerging new technologies, which will improve our understanding about the roles and mechanisms of herbal compounds in the regulation of inflammasomes and treatment of IBD.

[Effect of Yishen Tiaojing Recipe on hypogonadism induced by Tripterygium glycosides in women patients with nephropathy].

OBJECTIVE: To explore the effect of Yishen Tiaojing Recipe (YSTJR) on sex gland and kidney in nephropathy patients with hypogonadism induced by Tripterygium glycosides (TG). METHODS: Fifty-eight women patients with chronic glomerular disease were assigned to two groups, the 34 patients in the treated group were given TP 20 mg three times a day plus YSTJR, one dose daily, while the 24 in the control group were given TP 20 mg three times a day alone. The course of treatment lasted for 3 months. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), and luteotrophic hormone (LH), as well as urinary protein and red blood cell (RBC) count in urine were determined before and after treatment. RESULTS: Level of E2 decreased, FSH and LH increased in the control group after treatment (P < 0.05), while those indexes unchanged in the treated group. Quantity of urinary protein decreased in both two groups after treatment (P < 0.05), but the decrement was more significant in the treated group than in the control group (P < 0.05). Differences of all the above-mentioned indexes between the two groups after treatment were significant (all P < 0.05). CONCLUSION: YSTJR could prevent the injury of TP on sex gland in women patients with nephropathy, and is benificial for the treatment of primary chronic renal glomerular diseases.