Polycystic ovarian syndrome (PCOS) is an endocrine, metabolic, and systemic disease. It is mainly characterized by hyperandrogenism, oligomenorrhea, and high levels of luteinizing hormone (LH). There is no obvious therapy for PCOS, so patients have received symptomatic therapy. Welsh onion (Allium fistulosum) is well-known in Asian countries for its usage in food ingredients and traditional medicines. It is also studied for its many effects. These include activation of immune responses, antihypertensive effects, and antioxidant effects. Using letrozole-induced PCOS rats, we focused on herbal therapy using extract of Allium fistulosum (AF; A. fistulosum) roots to improve ovarian functions. As a nonsteroidal aromatase inhibitor, letrozole blocks conversion of testosterone to estrogen and subsequently induces PCOS phenomenon. We divided six-week-old female rats into four groups, including control, letrozole, letrozole + AF extract, and temporary letrozole groups. In our study, treatment with AF extract shows a low plasma LH/FSH ratio, and reveals high estrogen levels, ovarian morphology, folliculogenesis-related genes, and aromatase expression under PCOS mimic conditions. We concluded that AF extract administration influenced aromatase production, enhanced the estrogen steroid synthesis, and consequently restored the estrogenic feedback mechanism on the pituitary-ovary system.

Curcumae radix is the dry root of Curcuma longa L. (turmeric) that can be used either as a spice or traditional medicine. The aim of this study was to investigate the survival benefits and the anti-metastatic activity of curcumae radix extract (CRE) in MCF7 cells and in MMTV-PyMT transgenic mice—a mouse model of breast cancer metastasis. In vitro wound scratch assay revealed that CRE treatment inhibited cell motility and cell migration in a dose-dependent manner. To investigate the effect of CRE in breast cancer metastasis, MMTV-PyMT transgenic female virgin mice were used and randomly divided into two groups. For survival curve analysis, CRE was administered in a dose of 50 mg/kg to 8–20-week-old mice. Interestingly, CRE treatment significantly increased the median and prolonged survival of MMTV-PyMT mice. Furthermore, CRE treatment decreased tumor burden and inhibited cell proliferation in primary breast tumor, and also suppressed mammary tumor-derived lung metastasis. The size of the lung metastases substantially decreased in the CRE-treated group compared with the ones in the control group. Curcumae radix extract showed anti-metastatic activity through regulating the expression of metastasis markers including C-C Chemokine Receptor Type 7, Matrix Metalloproteinase 9 and the proto-oncogenes c-fos and c-jun. We demonstrated that these metastatic regulators were decreased when CCR7 expression was suppressed in MCF7 cells transfected with CCR7 siRNA. The results of this study show that curcumae radix exerts antitumor and anti-metastatic activities, and we suggest that curcumae radix might be a potential supplement for the treatment and prevention of breast cancer metastasis.

Pgrmc1 is a non-canonical progesterone receptor related to the lethality of various types of cancer. PGRMC1 has been reported to exist in co-precipitated protein complexes with epidermal growth factor receptor (EGFR), which is considered a useful therapeutic target in hepatocellular carcinoma (HCC). Here, we investigated whether Pgrmc1 is involved in HCC progression. In clinical datasets, PGRMC1 transcription level was positively correlated with EGFR levels; importantly, PGRMC1 level was inversely correlated with the survival duration of HCC patients. In a diethylnitrosamine (DEN)-induced murine model of HCC, the global ablation of Pgrmc1 suppressed the development of HCC and prolonged the survival of HCC-bearing mice. We further found that increases in hepatocyte death and suppression of compensatory proliferation in the livers of DEN-injured Pgrmc1-null mice were concomitant with decreases in nuclear factor κB (NF-κB)-dependent production of interleukin-6 (IL-6). Indeed, silencing of Pgrmc1 in murine macrophages led to reductions in NF-κB activity and IL-6 production. We found that the anti-proinflammatory effect of Pgrmc1 loss was mediated by reductions in EGFR level and its effect was not observed after exposure of the EGFR inhibitor erlotinib. This study reveals a novel cooperative role of Pgrmc1 in supporting the EGFR-mediated development of hepatocellular carcinoma, implying that pharmacological suppression of Pgrmc1 may be a useful strategy in HCC treatment.

Neurodegenerative diseases (ND) are being increasingly studied owing to the increasing proportion of the aging population. Several potential compounds are examined to prevent neurodegenerative diseases, including Curcumae radix, which is known to be beneficial for inflammatory conditions, metabolic syndrome, and various types of pain. However, it is not well studied, and its influence on energy metabolism in ND is unclear. We focused on the relationship between ND and energy metabolism using Curcumae radix extract (CRE) in cells and animal models. We monitored neurodegenerative markers and metabolic indicators using Western blotting and qRT-PCR and then assessed cellular glycolysis and metabolic flux assays. The levels of Alzheimer’s disease-related markers in mouse brains were reduced after treatment with the CRE. We confirmed that neurodegenerative markers decreased in the cerebrum and brain tumor cells following low endoplasmic reticulum (ER) stress markers. Furthermore, glycolysis related genes and the extracellular acidification rate decreased after treatment with the CRE. Interestingly, we found that the CRE exposed mouse brain and cells had increased mitochondrial Tricarboxylic acid (TCA) cycle and Oxidative phosphorylation (OXPHOS) related genes in the CRE group. Curcumae radix may act as a metabolic modulator of brain health and help treat and prevent ND involving mitochondrial dysfunction.

Journal of Biomedical and Translational Research

Background: Neurodegenerative diseases are increasingly being studied owing to the increasing proportion of the aging population. Several potential compounds have been studied to prevent neurodegenerative diseases, one of which is Curcumae Radix that is known to be beneficial for inflammatory conditions, metabolic syndrome, and various types of pain. However, it is not well studied and its influence on energy metabolism in neurodegenerative diseases is unclear. We focused on the relationship between neurodegenerative diseases and energy metabolism through Curcumae Radix extract in an animal model. Methods: Mice were treated with Curcumae Radix extract for 5 weeks orally 5 times in a week (50 mg/kg body weight). Murine delayed brain tumor (DBT) cells were supplemented with Curcumae Radix extract. We monitored the neurodegenerative makers and metabolic indicators using Western blotting and qRT-PCR and then assessed the cellular glycolysis and mitochondrial respiration through metabolic flux assay.Results: Low expression levels of Alzheimer’s disease-related markers were observed after treatment with Curcumae Radix extract. It was determined through the pAMPK/AMPK ratio that the ATP state was sufficient in the cerebrum and brain tumor cells. With this, an increase in glycolysis would be expected as glucose is the main energy source of the brain. However, glycolysis-related genes and the extracellular acidification rate showed that glycolysis decreased. Despite this, basal respiration and ATP production through mitochondrial respiration and increased TCA cycle and OXPHOS-related genes were observed in the Curcumae Radix group. Conclusions: In neurodegenerative diseases involving mitochondrial dysfunction, Curcumae Radix may act as a metabolic modulator of brain health to treat and prevent these diseases.