Efficacy and Mechanism of a Chinese Classic Prescription of Yueju in Treating Nonalcoholic Steatohepatitis and Protecting Hepatocytes from Apoptosis.

Yueju, a famous classic Chinese prescription, has been extensively used in treating depression syndromes for hundreds of years. Recent studies have reported that Yueju showed good effects in treating metabolic diseases, such as obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH), which leads to cirrhosis and severe cardiovascular diseases, is closely linked to obesity and abnormal lipid metabolism. In this study, Yueju could decrease the levels of alanine aminotransferase, aspartate transaminase, triglyceride, cholesterol, and low-density lipoprotein-C but increase the high-density lipoprotein-C in the serum of the NASH rat model induced by high-fat and high-cholesterol diet. Yueju could alleviate hepatosteatosis by increasing the phosphorylation of acetyl-CoA carboxylase and inhibiting the expression of fatty acid synthase and stearoyl-CoA desaturase 1. Yueju downregulated the expression of α-smooth muscle actin and collagen type 1A1, ameliorating the liver fibrilization. Yueju could also protect the hepatocytes from apoptosis by upregulating antiapoptosis protein Bcl-2 and X-linked inhibitor of apoptosis protein and downregulating apoptotic proteins Bax and cleaved poly ADP-ribose polymerase. Thus, Yueju could improve liver function, regulate lipid metabolism, alleviate hepatosteatosis and fibrosis, and protect hepatocytes from apoptosis against NASH. Yueju may be used as an alternative effective medicine for NASH treatment.

Treatment of murine colitis by Saccharomyces boulardii secreting atrial natriuretic peptide.

Inflammatory bowel disease is a lifelong disorder that involves chronic inflammation in the small and large intestines. Current therapies, including aminosalicylates, corticosteroids, and anti-inflammatory biologics, can only alleviate the symptoms and often cause adverse effects with long-term usage. Engineered probiotics provide an alternative approach to treat inflammatory bowel disease in a self-renewable and local delivery fashion. In this work, we utilized a yeast probiotic Saccharomyces boulardii for this purpose. We developed a robust method to integrate recombinant genes into the Ty elements of S. boulardii. Stable yeast cell lines that secreted various anti-inflammatory proteins, including IL-10, TNFR1-ECD, alkaline phosphatase, and atrial natriuretic peptide (ANP), were successfully created and investigated for their efficacies to the DSS-induced colitis in mice through oral administration. While IL-10, TNFR1-ECD, and alkaline phosphatase did not show therapeutic effects, the ANP-secreting S. boulardii effectively ameliorated the mouse conditions as reflected by the improvements in body weight, disease activity index, and survival rate. A post-mortem examination revealed that the ANP-treated mice exhibited significant downregulations of TNF-α and IL-1ß and an upregulation of IL-6 in colon tissues. This observation is consistent with the previous reports showing that TNF-α and IL-1ß are responsible for initiating the pathogenesis, whereas IL-6 plays a protective role in colitis. Overall, we demonstrated that S. boulardii is a safe and robust vehicle for recombinant protein delivery in the gastrointestinal tract, and ANP is a potential anti-inflammatory drug for colitis treatment. KEY MESSAGES: Recombinant genes can be robustly integrated into the transposable elements of S. boulardii. Oral administration of S. boulardii secreting IL-10 or TNF-α inhibitor did not exert therapeutic effects for DSS-induced colitis in mice. Atrial natriuretic peptide-secreting S. boulardii effectively ameliorated the murine colitis as reflected by improved body weight, disease activity index, and survival rate. The ANP-treated mice exhibited decreased mRNA levels of TNF-α and IL-1ß and an increased mRNA level of IL-6 in colon tissues.

[Acupoint injection of kakkonein for early- or mid-stage Parkinson's disease: a multicenter randomized controlled clinical trial].

OBJECTIVE: To investigate short- and long-term benefits and safety of acupoint injection of kakkonein for early- or mid-stage Parkinson's disease (PD). METHODS: A total of 135 patients with early- or mid-stage PD were enlisted and 116 cases completed the observation, including 40 cases in the acupoint-injection group, 37 cases in the acupuncture group and 39 cases in the medication group. Patients of the acupoint-injection group were treated by injection of kakkonein (2 mL) into bilateral Fengchi (GB 20), once very other day for 8 weeks. For acupuncture intervention, bilateral GB 20 acupoints were punctured with filiform needles, once every other day for 8 weeks. Patients of the medication group were treated by oral administration of compound levodopa (125 mg/time, twice a day) for 8 weeks. The disease severity was assessed by using Unified Parkinson's Disease Rating Scale (UPDRS, version 3. 0) before and after treatment, and one month after the treatment. RESULTS: After the treatment, scores of psychosis, behavior and emotion, daily life activity and motor function were all significantly decreased in the three groups in comparison with pre-treatment in each group (P<0.05), suggesting an improvement of the PD patients' conditions. The therapeutic effect of acupoint-injection and acupuncture groups was markedly superior to that of the medication group (P<0.05). One-month's follow-up showed that the scores of behavior-emotion and daily life activity were obviously lower in the acupoint-injection group than in the acupuncture and medication groups (P<0.05). No significant differences were found between the acupuncture and medication groups in down-regulating scores of behavior-emotion, daily life activity and motor function (P>0.05). CONCLUSION: Acupoint injection of kakkonein can improve patients' behavior, emotion, and daily life activity in early- or mid-stage PD patients and has both short- and longer-term benefits.