Flavonoids and phenolic acid are two of the rich polyphenols found in cinnamon (Cinnamomum zeylanicum). The effects of cinnamon extract on the inhibition of adipocyte differentiation in 3T3-L1 fibroblast cells and prohibitory lipid accumulation in male mice fed a high-fat diet were examined. Upon treating 3T3-L1 cells with cinnamon for 3 days, the cinnamon inhibited lipid accumulation and increased gene expression levels, such as those of adiponectin and leptin. In in vivo experiments, mice were randomized into four groups after a one-week acclimation period, as follows: normal diet, normal diet + 1% cinnamon extract, high-fat diet, and high-fat diet + 1% cinnamon extract. After 14 weeks of supplementation, we found that cinnamon extract increased the expression of lipolysis-related proteins, such as AMPK, p-ACC, and CPT-1, and reduced the expression of lipid-synthesis-related proteins, such as SREBP-1c and FAS, in liver tissue. Our results show that cinnamon extract may exhibit anti-obesity effects via the inhibition of lipid synthesis and adipogenesis and the induction of lipolysis in both 3T3-L1 fibroblast cells and mice fed a high-fat diet. Accordingly, cinnamon extract may have potential anti-obesity effects.

Aging and menopause are associated with oxidative stress and inflammation. Here, we evaluated the antioxidant properties of pumpkin (Cucurbita pepo L.) seed extract and assessed its ameliorative effects on aging- and menopause-related diseases using Saos-2 cells and ovariectomized rats. The seed extract had bioactive components that exhibited antioxidant activity. The extract increased the alkaline phosphatase (ALP) activity of Saos-2 cells. The oral administration of the extract to ovariectomized rats for 12 weeks decreased their body weight, fat weight, and cardiac risk indices. It also contributed to reductions in the levels of reactive oxygen species, oxidative stress, and inflammation, as assessed by measuring the serum levels of malondialdehyde and analyzing gene expression in rats. Furthermore, the administration of the extract also promoted an enhancement of the transcription of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (Ho-1), and catalase (Cat), involved in antioxidant activity; endothelial nitric oxide synthase (eNos), involved in vasculoprotective activity; and PR/SET domain 16 (Prdm16) and peroxisome proliferator-activated receptor-gamma coactivator (Pgc1α), involved in brown adipogenesis and thermogenesis. Our results using ovariectomized rats show that pumpkin seed extract may have ameliorative effects on menopause-related diseases by increasing ALP activity, evaluating the antioxidant system, ameliorating oxidative stress and thermogenesis, and enhancing lipid profiles.

Introduction: Kyung-Ok-Ko (KOK) is a popular traditional medicine used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms in Asia. Pueraria lobata Ohwi (P. lobata) is rich in isoflavones and has been traditionally used in combination with other herbs to produce synergistic and pharmaceutical effects via a multi-target approach for disease treatment. We aimed to investigate the phytoestrogenic effects of KOK extract against postmenopausal symptoms in ovariectomized (OVX) rats and confirm its efficacy by mixing KOK and P. lobata extracts.Methods: OVX rats were daily oral administrated with KOK and KOK + P. lobata mixture extracts (300–400 mg/kg) and their body weight and tail temperature were monitored for 12 weeks. The biochemical parameters, estradiol levels, and bone turnover markers were measured in the serum samples. Moreover, the estrogen receptor, ER-α and ER-β expression in the uterus and the uterus morphology were evaluated. AMPK, ATG1/ULK1, and mTOR protein expression in the liver were assessed.Results: The 12-week treatment with KOK and KOK + P. lobata mixture extracts did not cause liver damage or hormonal changes in the OVX rats. The treatments reduced the high lipid accumulation-related body weight gain and the tail temperature increase that was induced by ovariectomy. Further, it exhibited protective effects against hyperlipidemia and osteoporosis. No significant difference was observed in uterine weight compared to the OVX-treated group, while endometrial thickness reduction inhibition was observed due to ovariectomy. Bone mineral density (BMD) and serum osteocalcin levels, which decreased in OVX rats, increased with both treatments. Western blotting analysis showed that ER-α and ER-β were not expressed in the treated rats, whereas these proteins were expressed in Sham-operated rats. No significant differences in the phosphorylation of AMPK were observed; however, the ATG1/ULK1 and mTOR protein phosphorylation levels were upregulated and downregulated in the treated rats compared to those of OVX rats, respectively.Conclusion: This is the first in vivo study observing the efficacy and synergistic effects of the mixture of KOK and P. lobata. Our results suggest the potential of KOK and KOK + P. lobata mixture as an alternative therapy for alleviating menopausal symptoms.

Menopause is the natural period of aging in women induced by ovary deterioration, resulting in estrogen deficiency. We evaluated the antioxidative and anti-inflammatory properties of Cnidium officinale, Pueraria lobata Ohwi, and Leonurus japonicus (CPL) extracts on vascular endothelial dysfunction. After treatment, CPL extracts decreased serum lipid profiles, serum vasoactive substances, tail temperatures, and cardiovascular risk indices. In ovariectomized rats, vasodilation significantly increased, with an increase in endothelial nitric oxide synthase (eNOS) in the CPL200 and CPL500 groups compared with the OVX group (p < 0.05). The extracts also significantly reduced vascular cell adhesion protein 1 (VCAM-1) in the CPL50, CPL100, and CPL200 groups compared with the OVX group (p < 0.05, p < 0.01, and p < 0.001, respectively). Intercellular adhesion molecule 1 (ICAM-1) was also reduced in the CPL100 and CPL200 groups compared with the OVX group (p < 0.001 and p < 0.0001, respectively); this was achieved through the downregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide (iNOS), which resulted in the synthesis of nuclear factor erythroid 2-related factor 2 (NRF2) and eNOS in HUVECs. Our results show that CPL extracts could provide cardioprotective effects against vascular endothelium dysfunction by decreasing inflammation and upregulating vasodilation, ascertained by evaluating the antioxidant systems of ovariectomized rats. Further studies are needed to explore the long-term cardioprotective effects.

A single-nucleotide missense polymorphism (rs1800449, R158Q) in the propeptide domain of lysyl oxidase (LOX-PP) is associated with increased risk of coronary artery disease (CAD) independent of changes in plasma lipid levels. Although the enzymatic function of LOX has an essential role for the cross-linking of extracellular matrix proteins in connective tissues, whether and how LOX-PP R158Q contributes to the development of atherosclerosis has not been clearly established. Here, hypercholesterolemia was induced in mice that were WT or homozygous for the LOX-PP R158Q polymorphism by adeno-associated virus-8–mediated overexpression of Pcsk9 followed by high-fat diet feeding for 16 weeks. We found that the R158Q polymorphism promoted atherosclerosis and induced proliferation of macrophages and vascular smooth muscle cells without altering LOX enzymatic activity. Using single-cell RNA sequencing, we found the transcriptional program of atherosclerotic plaques from mice harboring R158Q was strongly enriched for proliferation- and calcification-related genes in a regionally distinct manner. Together, these results establish an enzymatically independent proatherogenic role for the LOX-PP and suggest its potential as a novel therapeutic target.