Efficacy and Safety of the Chinese Herbal Compound TJAOA101 in Treating Diminished Ovarian Reserve: A Protocol for Multicenter, Prospective, and Pre-Post Study.

OBJECTIVE: Diminished ovarian reserve (DOR) can lead to early menopause, poor fecundity, and an increased risk of disorders such as osteoporosis, cardiovascular disease, and cognitive impairment, seriously affecting the physical and mental health of women. There is still no safe and effective strategy or method to combat DOR. We have developed a novel Chinese herbal formula, Tongji anti-ovarian aging 101 (TJAOA101), to treat DOR. However, its safety and efficacy need to be further validated. METHODS: In this prospective and pre-post clinical trial, 100 eligible patients aged 18-45 diagnosed with DOR will be recruited. All participants receive TJAOA101 twice a day for 3 months. Then, comparisons before and after treatment will be analyzed, and the outcomes, including anti-mullerian hormone (AMH) and follicle-stimulating hormone (FSH) levels and the antral follicle count (AFC), the recovery rate of menopause, and the Kupperman index (KMI), will be assessed at baseline, every month during medication (the intervention period), and 1, 3 months after medication (the follow-up period). Assessments for adverse events will be performed during the intervention and follow-up periods. CONCLUSION: A multicenter, prospective study will be conducted to further confirm the safety and efficacy of TJAOA101 in treating DOR and to provide new therapeutic strategies for improving the quality of life in DOR patients.

Baicalin Blocks Colon Cancer Cell Cycle and Inhibits Cell Proliferation through miR-139-3p Upregulation by Targeting CDK16.

Baicalin was reported to facilitate the apoptosis of colon cells and inhibit tumor growth in vivo. This study aimed to explore the specific mechanism and function of baicalin on colon cells. Relative mRNA levels were tested via qPCR. Cell proliferation, viability, and cell cycle phases were evaluated using MTT, colony formation, and flow cytometry assays, respectively. The interaction between miR-139-3p and cyclin-dependent kinase 16 (CDK16) was measured via a dual-luciferase reporter assay. Immunohistochemistry was used to count the positivity cells in tumor tissues collected from treated xenografted tumor mice. The results showed that baicalin increased miR-139-3p expression while also decreasing CDK16 levels, blocking the cell cycle, and inhibiting cell proliferation in colon cancer cells. miR-139-3p silencing or CDK16 overexpression abolished the inhibitory effects of baicalin on colon cancer proliferation. miR-139-3p directly targeted and interacted with CDK16 at the cellular level. The protective functions of miR-139-3p knockdown on tumor cells were abrogated by silencing CDK16. The combination of baicalin treatment and CDK16 knockdown further inhibited tumor growth of xenografted tumor mice compared with the groups injected with only sh-CDK16 or baicalin in vivo. In conclusion, baicalin inhibited colon cancer growth by modulating the miR-139-3p/CDK16 axis.

Sesquiterpenes and polyphenols with glucose-uptake stimulatory and antioxidant activities from the medicinal mushroom Sanghuangporus sanghuang.

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 µmol·L-1, respectively. Compounds 9-12 also showed good cellular antioxidant activities with CAA50 values of 12.23, 23.11, 5.31 and 16.04 µmol·L-1, respectively. Molecular docking between COVID-19 Mpro and compounds 9-12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods.

[Prevention and Treatment of Shenkang Injection for Contrast-induced Nephropathy in Elder Patients with Chronic Kidney Disease].

Objective To explore the safety and effectiveness of Shenkang Injection (SI) for con- trast-induced nephropathy (CIN) in elderly patients with chronic kidney disease (CKD). Methods Totally 206 elderly CKD patients who were scheduled to undergo coronary angiography (CAG) were assigned to three groups according to random digit table, i.e., the rehydration therapy group (67 cases) , the SI group (71 cases) , and the control group (68 cases). Patients in the rehydration therapy group received intrave- nous dripping of normal saline 12 h before and after CAG. Patients in the SI group received intravenous drip- ping of SI, while those in the control group received intravenous dripping of 5% glucose injection. SI and 5% glucose injection was respectively used 3 days before CAG and 4 days after CAG, once per day. The inci- dence rate of CIN, and levels of creatinine, blood urea nitrogen (BUN) , serum cystatin C (CysC), kidney injury molecule-1 (KIM-1), and P2-microglobulin (P2-MG) were detected before CAG, 24 h and 96 h after CAG, respectively. Age, sex, SI, contrast dose, pre-CAG indicators of renal function were compared. Their correlations with changed 24-h creatinine value (the difference between the value at post-CAG 24 h and pre-CAG) and CIN incidence rate were analyzed using Sperman correlation and Logistic regression analy- ses. Results Compared with the rehydration therapy group and the control group, the incidence rate of CIN was significantly lower in the SI group (x2 = 5. 32, P <0. 05). Compared with before treatment in the same group, levels of creatinine and CysC were all elevated in the 3 groups after 24-and 96-h treatment (P <0. 05) ; the KIM-1 level increased in rehydration therapy group and the control group (P <0. 05) ; P2-MG level increased in the SI group (P <0.05). Compared with the control group, post-CAG P2-MG level in- creased in the SI group (P <0. 05). There was no statistical difference in other index (P >0. 05). SI was neg- atively with the incidence rate of CIN and changed 24-h creatinine value (r = -0. 612, -0. 517, P <0. 05). The contrast dose was positively with the incidence rate of CIN and changed 24-h creatinine value (r = 0. 644, 0. 562, P <0. 05). Increased contrast dose could elevate the incidence rate of CIN (P <0. 05). SI could obviously lower the incidence rate of CIN (P <0. 05). Conclusion SI could lower the incidence rate of CIN in elder CKD patients by playing certain roles in prevention and treatment.

Rosmarinic acid inhibits proliferation and induces apoptosis of hepatic stellate cells.

Hepatic stellate cells (HSCs), activated during liver injury, are defined as the most important target in the therapy of hepatic fibrosis. In the present study, we evaluated the effect of Rosmarinic acid (RosA) on the proliferation and apoptosis in activated hepatic stellate cells (HSC-T6), which is useful to decrease this cell population. The proliferation of HSC-T6 was significantly inhibited after treated with various concentrations of RosA for different times. Flow cytometric analyses and transmission electron microscope (TEM) observations revealed that HSC-T6 treated with RosA underwent apoptosis in a time dependent manner and displayed typical apoptotic features in the cells. The phosphorylation in signal transducer and activator of transcription protein-3 (STAT3), which regulates cell survival, proliferation and differentiation in a variety of tissues, was markedly decreased as the result of Western blot assay and correlated with downregulation of CyclinD1 and B cell lymphoma/leukemia-2 (Bcl-2). In conclusion, these results suggested that RosA was able to inhibit proliferation and induce apoptosis in HSC-T6, partly due to the inhibition of phosphorylation in STAT3, which contributed to the reversal of hepatic fibrosis.

[Effect of bushen antai recipe and its various compositions on endometrial sexual hormones and receptors in mice with blastocyst implantation dysfunction].

OBJECTIVE: To compare the effects and mechanisms of Bushen Antai Recipe (BAR) and its different compositions, Bushen Recipe (BSR, the Shen-nourishing part) and Huoxue Recipe (HXR, the blood-activating part) on the endometrial receptivity in mice with blastocyst implantation dysfunction (BID). METHODS: Model mice of BID induced by indomethacin were treated respectively with BAR, BSR and HXR from the first day of pregnancy, and killed on day 5 or 6. Samples of their serum and uterine were collected for detecting serum estradiol (E2), progesterone (P) contents using radioimmunoassay; and endometrial expression levels of their receptors, ER and PR, using immunohistochemistry. RESULTS: Serum levels of E2 and P, and endometrial expression of ER and PR increased significantly on day 6 in mice after treated by BAR, but in those treated by BSR and HXR, the improvements were significantly lesser. CONCLUSION: BAR, by combined application of both Shen-nourishing and blood-activating methods, could impact E2, P, ER and PR to improve the endometrial receptivity to a higher extent in BID mice so as to promote embryo implantation.

[Preparation of coated tablets of glycyrrhetic acid-HP-beta-cyclodextrin tablets for colon-specific release].

OBJECTIVE: To prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release. METHOD: In order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties. RESULT: The formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%. CONCLUSION: The preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.