Discovery of a novel, liver-targeted thyroid hormone receptor-ß agonist, CS271011, in the treatment of lipid metabolism disorders.

Introduction: Thyroid hormone receptor ß (THR-ß) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-ß agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. Methods: We conducted luciferase reporter gene assays to assess the activation of THR-ß and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. Results: Compared with MGL-3196, CS271011 showed higher THR-ß activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. Conclusions: CS271011 is a potent and liver-targeted THR-ß agonist for treating lipid metabolism disorders.

(+)- and (-)-Xanthostones A-D: Four Pairs of Enantiomeric Cinnamoyl-ß-Triketone Derivatives from Xanthostemon chrysanthus.

Four pairs of cinnamoyl-ß-triketone derivative enantiomers, (+)- and (-)-xanthostones A-D ((+)- and (-)-1-4), were isolated from Xanthostemon chrysanthus. Compounds 1 and 2 feature a new rearranged cinnamoyl-phloroglucinol scaffold fused with a cinnamyl-ß-triketone framework. Compounds 1, 3, and 4 are the first examples of natural products with a peculiar phenethyl-pyranone acid unit. Their structures with absolute configurations were determined by spectroscopic data, X-ray diffraction analysis and electronic circular dichroism (ECD) calculation. Interestingly, these novel compounds showed a tautomeric behavior in solution, which was revealed by NMR spectroscopy and density functional theory calculation. A plausible biosynthetic pathway toward xanthostones A-D was proposed. Additionally, the anti-inflammatory and antibacterial activities of xanthostones A-D were evaluated.

[Animal model analysis of knee osteoarthritis based on clinical characteristics of Chinese and Western medicine].

Knee osteoarthritis(KOA) is a common orthopedic disease. Its main symptoms include pain in the medial knee, aggravated knee pain during walking, limited movement, and joint deformity, which seriously affect the daily life of patients. The replication of animal models consistent with clinical symptoms is the premise of KOA-related experimental research. Based on the clinical characteristics of KOA and Western medicine, this paper discusses the existing KOA animal model, and analyzes the clinical anastomosis of the existing model based on the clinical diagnostic criteria of KOA. Through analysis and comparison, it can be seen that most of the existing modeling methods are single-factor animal models, which have a certain gap with the characteristics of KOA caused by clinical multi-factors and interaction. Moreover, modeling methods are mostly guided by Western medicine, and traditional Chinese medicine pathogenic factors are absent in the modeling process. Only cold stimulation method takes cold and wet into account. In the evaluation of the model, knee swelling, pain and articular rickets were the main evaluation criteria, which were different from the diagnostic criteria of Chinese and Western medicine in KOA. In terms of syndrome differentiation and classification, KOA is divided into kidney vacuity and deficiency of marrow, Yang vacuity and cold coagulation, and blood stasis and arrest in traditional Chinese medicine. The exis-ting animal models often confuse KOA with each other. Only cold stimulation method is used to establish KOA of Yang vacuity and cold coagulation. Therefore, in this paper, based on KOA clinical symptoms between Chinese and Western medicine features, analysis of the existing animal models, for further improving KOA animal models, the standardization of the model to evaluate suggestions, in order to improve the animal models and clinical inosculation between Chinese and Western medicine, the KOA animal model to better serve the scientific research work, promote the related mechanism, pathological changes and drug screening.

Effect of stachydrine hydrochloride to the prostate hyperplasia model in mice.

Study the effect of stachydrine hydrochloride to prostatic hyperplasia in mice which made of the urogenital sinus implantation. KM male mices were selected. The group was given the respective drugs for gavage, the group of BG and MG were given the distilled water which the same amount as the drugs group for 21 consecutive days. The level of DHT, ACP, Non PACP were measured in serum, the average wet weight of the prostate and prostate index were calculated, the expression of bFGF, EGF, IGF-I, TGF-ß in prostate tissue were measured, the pathological changes of the prostate, kidney, thymus, spleen were observed by HE staining. Compared with MG, stachydrine hydrochloride high (SHH), medium (SHM) and low (SHL) group could reduced the level of DHT and PACP in serum significantly (P < 0.01); SHM and SHL could increased the express of TGF-ß1 significantly (P < 0.05); SHH, SHM, SHL could reduced the express of EGF significantly (P < 0.01); SHM could reduced the express of IGF-Ⅰ significantly (P < 0.01); Compared with MG, SHH, SHM, SHL could reduced the pathological changes of prostate significantly (P < 0.01); FG could reduced the kidney pathological changes significantly (P < 0.01). Stachydrine hydrochloric had no significant effect on the kidney. Stachydrine hydrochloride had the effect of improve thymus, spleen pathological changes. Stachydrine hydrochloride has a good inhibition effect on prostatic hyperplasia model in mices.

[Study on function evaluation of health food containing Chinese materia medica based on data mining].

Homology of medicine and food is an important content in Chinese medicine and also works as the basis for guiding the development of compound health food containing Chinese materia medica. The top products,supplements,health care prescriptions,and medicinal meals in traditional herbal texts are the theoretical treasures of Chinese medicine compound health foods. With the implementation of the National Healthy China 2030,China's major health industry faces with tremendous opportunities. It is necessary to develop a batch of compound health food containing Chinese materia medica with Chinese medicine characteristics,in line with the needs of the country and society. Domestic research on compound health food containing Chinese materia medica mainly focuses on the extraction of functional components,preparation molding processes,quality standards,and efficacy evaluation. However,there are still some deficiencies in the related characteristics of traditional Chinese medicine(TCM) theory and function,evaluation criteria of efficacy and safety,new product R&D evaluation system and R&D platform. Based on a large number of previous studies by this laboratory,the views in nature,flavor and efficacy relationship were put forward in this paper. Based on the establishment of the Chinese medicine function-pharmacology-clinical application database system,the Chinese medicine compatibility database system,the Chinese medicine nature and flavor modern research database system,and the evaluation platform for animal models of Chinese medicine; the efficacy study,safety evaluation system,new product research and development evaluation system as well as research and development platform were established,providing a basis for the development and evaluation of compound health food containing Chinese materia medica. The modern scientific connotation of the core efficacy of compound health food containing Chinese materia medica was explained as well,helpful to promote the research and development of compound health food containing Chinese materia medica and play an important role in general health.

Study on neuroendocrine-immune function of Phenylethanoid Glycosides of Desertliving Cistanche herb in perimenopausal rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Desertliving Cistanche herb was first recorded in "Shen Nong'Herbal Classic" and listed as the top grade herbal medicine in it. Phenylethanoid glycosides are indicative components for identification and content determination of Desertliving Cistanche herb in Chinese pharmacopoeia, which is also one of the main active components. In this research, we explored the mechanism of phenylethanoid glycosides of Desertliving Cistanche herb to the perimenopausal model rats. AIM: The purpose of this study is to research the effects of phenylethanoid glycosides of Desertliving Cistanche herb (PGC) on the neuroendocrine-immune function of perimenopausal syndrome by perimenopausal model rats. MATERIALS AND METHODS: Wistar female rats were selected. The left ovaries for all rats except in the blank control group(BC) were removed, and the right ovaries were removed in 80%. The vaginal smear showed irregular estrous cycle changes for the perimenopausal model rats. And the perimenopausal model rats were gavaged Gengnian'an, Phenylethanoid Glycosides of Desertliving Cistanche herb high, medium, low suspension which is 450mg/(kg day), 133.33mg/(kg day), 66.67mg/(kg day), 33.33mg/(kg day); the group of BC and model group (MC)were given distilled water in the same volume as the drugs group for 30 consecutive days. Horizontal-vertical exercise scores were measured at 29 days of dosing. After the last administration, the blood was taken from the abdominal aorta, and levels of E2, LH, FSH, GnRH, BGP in serum, and the levels ß-EP in plasma were measured respective. Organ indexes of thymus, spleen, and uterus were calculated. The content of estrogen receptor (ER) in the hypothalamic, pituitary and uterus tissues and the content of androgen receptor (AR) in the hypothalamic homogenate were measured. The pathological changes of the thymus, spleen, uterus, ovary were observed by HE staining. RESULTS: Compared with MC, PGC increase the activity, the organ index (thymus, spleen, uterus), E2, T, BGP level in serum, ß-EP level in plasma, AR level in hypothalamus, ER level in hypothalamus, pituitary, uterus in perimenopausal model rats. And it also reduced FSH, LH, GnRH level in serum, and improved uterine and ovarian lesions in perimenopausal model rats. CONCLUSION: Each dose of PCG could counteract the disorder of sex hormone in perimenopausal model rats, correct the imbalance of ER and AR level, enhance and restore the effect of uterus and the nerve cells of hypothalamic, and improve immune function.

The antioxidant activity and nitric oxide production of extracts obtained from the leaves of Chenopodium quinoa Willd.

BACKGROUND: Most reports have indicated the antioxidant capacity of quinoa seeds. However, the leaves of Quinoa (Chenopodium quinoa Willd.) are usually worthless and little known about their biological activities. In this study, the antioxidant and immunomodulatory potential of the quinoa leaf extracts were explored. METHODS: The crude leaf extracts of quinoa were extracted using water, 50% ethanol or 95% ethanol as solvent, denoted WQL, 50% EQL and 95% EQL, respectively. The antioxidant activities of quinoa leaf extracts were assessed by the ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging and iron chelating. The total phenolic content was determined. Inhibition of nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells was examined to gauge the anti-inflammatory activity. RESULTS: The 95% EQL showed a higher level of total phenolic content (569.5 mg GAE/g extract) and better DPPH scavenging activity. The WQL exhibited a better iron chelating capacity (28.9% at 10 mg/ml). The iron chelating activity of the 95% EQL increased in a concentration-dependent manner, which ranged from 10.9% up to 53.9%. The 50% EQL and 95% EQL significantly inhibited NO production in the LPSstimulated RAW 264.7 cells. CONCLUSION: We demonstrate that the extracts of quinoa leaves possess the biological activities of antioxidant and anti-inflammatory. Our finding suggests that the leaf extract of quinoa has potential to be utilized for natural health products.