Niaj Morshed

Stauntonia hexaphylla (Thunb.) Decne (SH), a medicinal plant from the Lardizabalaceae family, holds traditional importance in East Asia for treating rheumatism. Steam treatment is commonly applied to enhance its medicinal properties, but the chemical and biological changes resulting from this process remain unexplored. This study compared steamed and untreated SH fruit (SHF) extracts, analyzing their chemical composition, antioxidant activity, and effects on bone health using in vitro models. Steamed SHF extracts exhibited increased levels of 5-hydroxymethylfurfural (5-HMF), total flavonoids, phenolics, and enhanced antioxidant activity. Bone health assessment using osteoclasts differentiated from RAW 264.7 cells and osteoblasts from MC3T3-E1 cells revealed that steamed extracts promoted alkaline phosphatase activity, calcium nodule formation, and collagen synthesis in osteoblasts while inhibiting tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts. Additionally, steamed SHF extracts effectively modulated gene expression related to osteoclastogenesis and osteoblastogenesis by downregulating TRAP, NFTAc1, RANK, MMP9, c-Fos, and TRAF6 while upregulating ALP, Runx2, BGLAP, Col1a1, and OPG. The component 5-HMF played a pivotal role in promoting alkaline phosphatase and inhibiting TRAP activities. These findings suggest that steamed SHF may offer a promising therapeutic approach for postmenopausal osteoporosis.

Stauntonia hexaphylla (Thunb.) Decne (SH) is known for its anti-inflammatory, analgesic, antioxidant, and anti-osteoporotic properties. This study investigated the composition of SH leaves and fruits and assessed their individual and combined effects in an in vitro osteoporosis model. Extracts with varying leaf-to-fruit ratios (SH82, SH55, SH28) were evaluated in MC3T3-E1 and RAW264.7 cells to examine osteogenesis and bone resorption biomarkers. SH leaves were rich in chlorogenic acids (CGAs) and flavonoids, while fruits contained phenolic acids with minimal flavonoids. Leaf extracts exhibited superior antioxidant activity and ROS suppression. Both leaf and fruit extracts enhanced ALP activity, calcium deposition, and collagen formation in MC3T3-E1 cells, with leaf extracts demonstrating greater efficacy. Additionally, osteoblastogenesis-related genes were upregulated, while TRAP activity and osteoclast-related gene expression were significantly inhibited. The combined extract exerted a synergistic effect, with SH28 showing the most pronounced osteogenic enhancement and TRAP inhibition. Key components, including neo-CGA, CGA, rutin, and luteolin-7-O-glucoside, positively influenced ALP and TRAP activities. These findings highlight the potential of SH, particularly at a high leaf-to-fruit ratio, as a promising natural agent for osteoporosis prevention.

Background: Ginsenoside-CK (G-CK), a bioactive molecule found in Korean Panax ginseng Meyer. According to recent studies, CK exhibits a broad range of pharmacological actions. In this study, we investigated the G-CK's anticancer efficacy using both in-silico and in-vitro approaches. Our investigation predicted that G-CK can suppress kidney and colon cancer by suppressing gene targets such as PHLDA1, PHLDA2, and PHLDA3. Materials & Methods: We performed in-silico investigation and G-CK exhibited a strong affinity for each of the three target proteins' binding sites. We used 150 ns of molecular dynamics (MD) simulations to evaluate G-CK's stability, followed by cytotoxicity assays, RT-PCR, and qRT-PCR validation. Results: Based on its stable and favorable energies, G-CK demonstrated strong binding to the targets, as demonstrated by free energy calculations and MD simulations. Similarly, G-CK reduced the PHLDA gene family's (PHLDA1, PHLDA2, and PHLDA3) mRNA expression in A498, HT-29 cells at 10 μg/mL, as well as normal cells HEK-293 and RAW 264.7, without substantial cytotoxicity. Lastly, G-CK treatments resulted in a significant decrease in PHLDA gene family expression, confirmed by RT-PCR and qRT-PCR results. Conclusion: Thus, we can conclude that G-CK suppresses the expression of PHLDA gene family gene targets, hence regulating kidney and colon cancer.

The present study explored the possible antiobesogenic and osteoprotective properties of the gut metabolite ginsenoside CK to clarify its influence on lipid and atherosclerosis pathways, thereby validating previously published hypotheses. These hypotheses were validated by harvesting and cultivating 3T3-L1 and MC3T3-E1 in adipogenic and osteogenic media with varying concentrations of CK. We assessed the differentiation of adipocytes and osteoblasts in these cell lines by applying the most effective doses of CK that we initially selected. Using 3T3-L1 adipocytes in vitro assessments, CK could effectively decrease intracellular lipid accumulation, inhibit α-glucosidase enzyme, increase 2-NBDG glucose uptake, reduce inflammation-associated cytokines (TNFα, and IL-6), adipogenic regulatory genes (PPARγ, FAS, C/EBPα), lipogenic gene LPL, and increase the expression of thermogenic gene UCP1. Additionally, CK treatment induced osteoblast development in MC3T3-E1 cells as shown by increased mineralization and calcium distribution, collagen content, alkaline phosphatase activity, and decreased inflammatory cytokines TNFα, and IL-6 and increased the regulated expressions of osteogenic genes including Runx2, ALP, BGLAP, OCN, and Col1a1. Significantly, as a major inhibitory regulator, the TP⁵³ gene was down-regulated in both 3T3-L1 and MC3T3E1 cells after the treatment of CK. These encouraging results demonstrate the possible use of CK as an innovative treatment for controlling obesity and osteoporosis, targeting the underlying mechanisms of obesogenic and bone loss. Further studies are necessary to explore the clinical implications of these results and the potential of CK in future treatment strategies. This research highlights the promise of CK in addressing significant health issues.

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE’s mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography–mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERβ, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/β-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.

The PHLDA (pleckstrin homology-like domain family) gene family is popularly known as a potential biomarker for cancer identification, and members of the PHLDA family have become considered potentially viable targets for cancer treatments. The PHLDA gene family consists of PHLDA1, PHLDA2, and PHLDA3. The predictive significance of PHLDA genes in cancer remains unclear. To determine the role of pleckstrin as a prognostic biomarker in human cancers, we conducted a systematic multiomics investigation. Through various survival analyses, pleckstrin expression was evaluated, and their predictive significance in human tumors was discovered using a variety of online platforms. By analyzing the protein–protein interactions, we also chose a collection of well-known functional protein partners for pleckstrin. Investigations were also carried out on the relationship between pleckstrins and other cancers regarding mutations and copy number alterations. The cumulative impact of pleckstrin and their associated genes on various cancers, Gene Ontology (GO), and pathway analyses were used for their evaluation. Thus, the expression profiles of PHLDA family members and their prognosis in various cancers may be revealed by this study. During this multiomics analysis, we found that among the PHLDA family, PHLDA1 may be a therapeutic target for several cancers, including kidney, colon, and brain cancer, while PHLDA2 can be a therapeutic target for cancers of the colon, esophagus, and pancreas. Additionally, PHLDA3 may be a useful therapeutic target for ovarian, renal, and gastric cancer.

Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

Rare ginsenoside compound K (CK), is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development as well as ginsenosides-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bio-conversion processes. Current research shows that CK has a wide range of pharmacological actions including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, anti-inflammatory, and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signal-ing pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on nonalcoholic fatty liver disease, obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.