Zuogui and Yougui pills improve perimenopausal syndrome regulation of apoptosis in mice.

OBJECTIVE: To examine, dissect, and understand the molecular mechanisms and combinatorial effects of Zuogui (, ZGP) and Yougui pills (, YGP) in 4-vinyl cyclohexene diepoxide (4-VCD)-induced Perimenopausal syndrome (PMS). METHODS: Using the 4-VCD-induced PMS mouse model, uterine and ovary index were measured, and serum sex steroidal hormone levels were evaluated after treatment with ZGP, YGP, ZGP + YGP, estradiol valerate (EV), and Gengnian An (gengnianan, GNA). Histopathological examinations, ingredient-target network predictions, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed to ascertain the possible pharmacological effects and molecular mechanisms of ZYP and YGP. RESULTS: Treatment with ZGP and YGP remarkably improves estrous cyclicity and prevents pathological damage to the uterus. Also, altered sex hormones, including AMH, E2, FSH, LH, P, and T, were restored to normal levels after ZGP and YGP administration. Ingredient-target network analysis showed that the 5 ingredients common to the ZGP and YGP formula modulate 53 targets shared with PMS. Pathway-enrichment analysis further predicted that ZGY and YGP likely regulate of apoptosis and other essential pathways during PMS. In-vivo studies showed that ZGP and YGP suppress PMS modulating apoptosis through decreasing Caspase-3 and Bcl-2-associated X (Bax) levels and increasing B-cell lymphoma-2 (Bcl-2)/Bax and Bcl-2 levels. Importantly, ZGP + YGP treatment modulation effects were somewhat or significantly better compared to ZGP or YGP alone treatment. CONCLUSION: ZGP and YGP represent novel anti-PMS agents whose effects involve restoring altered hormonal levels, protecting the uterus, and regulating apoptosis.

[Neuroprotective effect of cinnamaldehyde in MPTP-induced mouse model of subacute Parkinson's disease].

This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA) in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD) and the mechanism. To be specific, male C57 BL/6 mice(n=72, SPF) were randomized into control group, model group, positive control(madopar 0.1 mg·g~(-1)) group, and low-dose, me-dium-dose, and high-dose CA groups(0.15, 0.30, 0.60 mg·g~(-1)). MPTP(intraperitoneal injection, 0.03 mg·g~(-1), once a day for 5 days) was used to induce subacute PD in mice except for the control group. The administration began from the day of modeling and lasted 19 days. On the 0 th, 12 th, and 19 th day, the open field test, pole test, and rotarod test were carried out. After the tests, the mice were killed and brains were separated. In addition, the organ index was measured. The number of cells in substantia nigra(SN) in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE) staining. The levels of tyrosine hydroxylase(TH)-and α-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining, and the protein levels of TH and α-Syn in SN by Western blot. The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair, arched back, rigidity of the tail, slow movement, and tremor, decreased number of crossings and rearing, increased frequency of urination and defecation, longer time of pole climbing, and shorter time of staying on the rotating rod. In addition, the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking. In addition, the average optical density of TH in SN decreased and that of α-Syn increased. All these suggested the successful modeling. CA displayed obvious therapeutic effect on the PD mice, as manifested by the increased number of crossings and rearing, decreased frequency of urination and defecation, shorter time of climbing pole, longer time of staying on the rotating rod, and more neuron cells in the SN with a few pykno-tic cells. Moreover, CA significantly alleviated the decrease of TH and the overexpression of α-Syn in SN. As a result, the MPTP-induced injury of dopaminergic neurons was alleviated. The performance of 0.3 mg·g~(-1) CA was the best. This study is expected to lay a scientific basis for the development of CA products.

1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis.

NOD-like receptor (NLR) family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in inflammation-associated diseases such as multiple sclerosis, Parkinson's disease, and stroke. Targeting the NLRP3 inflammasome is beneficial to these diseases, but few NLRP3 inflammasome-selective inhibitors are identified to date. Essential oils (EOs) are liquid mixtures of volatile and low molecular-weight organic compounds extracted from aromatic plants, which show various pharmacological activities, including antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory properties. In this study we screened active ingredients from essential oils, and identified 1,2,4-trimethoxybenzene (1,2,4-TTB) as a selective NLRP3 inflammasome inhibitor. We showed that 1,2,4-TTB (1 mM) markedly suppressed nigericin- or ATP-induced NLRP3 inflammasome activation, thus decreased caspase-1 activation and IL-1ß secretion in immortalized murine bone marrow-derived macrophages (iBMDMs) and in primary mouse microglia. Moreover, 1,2,4-TTB specifically inhibited the activation of NLRP3 inflammasome without affecting absent in melanoma 2 (AIM2) inflammasome activation. We further demonstrated that 1,2,4-TTB inhibited oligomerization of the apoptosis-associated speck-like protein containing a CARD (ASC) and protein-protein interaction between NLRP3 and ASC, thus blocking NLRP3 inflammasome assembly in iBMDMs and in primary mouse macrophages. In mice with experimental autoimmune encephalomyelitis (EAE), administration of 1,2,4-TTB (200 mg · kg-1 · d-1, i.g. for 17 days) significantly ameliorated EAE progression and demyelination. In conclusion, our results demonstrate that 1,2,4-TTB is an NLRP3 inflammasome inhibitor and attenuates the clinical symptom and inflammation of EAE, suggesting that 1,2,4-TTB is a potential candidate compound for treating NLRP3 inflammasome-driven diseases, such as multiple sclerosis.

Association of Serum Vitamin C With NAFLD and MAFLD Among Adults in the United States.

BACKGROUND AND AIMS: Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals. METHODS: Herein, the nationally representative National Health and Nutrition Examination Survey 2017-2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0-F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC. RESULTS: A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5-67.0 µmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9-50.5 µmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively. CONCLUSION: In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases.

Research Progress on Prevention and Treatment of Cognitive Dysfunction in Diabetes Mellitus with Traditional Chinese Medicine / 中国实验方剂学杂志

Diabetes is a lifelong non-communicable disease caused by continuous high blood sugar,which poses a great threat to people's health. Diabetic cognitive dysfunction is the neurological impairment caused by the disorder of glucose and lipid metabolism in diabetes mellitus,which is characterized by inattention,decreased learning and memory ability,and then developed into alzheimer's disease.The pathogenesis of diabetic cognitive dysfunction is not fully understood.there are no effective drugs for this disease, hypoglycemic drugs are mainly used in the clinical treatment of diabetic cognitive dysfunction,and most drugs are accompanied by serious adverse reactions while playing a therapeutic role,drug resistance and liver injury are easy to occur.In recent years,there have been a lot of research achievements on the prevention and treatment of cognitive dysfunction in diabetes mellitus with traditional Chinese medicine(TCM).Modern medicine believes that diabetes belongs to the category of consumptive thirst of TCM, and the diabetic cognitive dysfunction is consumptive thirst combined with dementia and forgetfulness.Qi and Yin deficiency runs through the whole process of consumptive thirst,the Qi injured,Then the Qi defficiency would cause blood circulation malfunction, long-time poor blood condition would cause blood stagnating in the brain and blocking the brain,which would lead to the brain disease.TCM can improve the diabetic cognitive dysfunction by lowering blood sugar,inhibiting neuron damage, deposition of Amyloid beta(Aβ)and abnormal phosphorylation of Tau protein.This article reviews the pathogenesis of diabetic cognitive dysfunction from glucolipid metabolic disorders,disruption of blood brain barrier,inflammation,oxidative stress and non enzymatic glycosylation,insulin resistance in diabetes etc.,and explores the prevention and treatment of diabetic cognitive dysfunction by Chinese medicine,to provide a reference for the research and development of drug prevention and treatment of diabetic cognitive dysfunction.