Anti-osteoporotic Properties Research Articles

Onion (Allium cepa L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.

Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.

Integrated machine learning-based virtual screening and biological evaluation for identification of potential inhibitors against cathepsin K.

Cathepsin K is a type of cysteine proteinase that is primarily expressed in osteoclasts and has a key role in the breakdown of bone matrix protein during bone resorption. Many studies suggest that the deficiency of cathepsin K is concomitant with a suppression of osteoclast functioning, therefore rendering the resorptive properties of cathepsin K the most prominent target for osteoporosis. This innovative work has identified a novel anti-osteoporotic agent against Cathepsin K by using a comparison of machine learning and deep learning-based virtual screening followed by their biological evaluation. Out of ten shortlisted compounds, five of the compounds (JFD02945, JFD02944, RJC01981, KM08968 and SB01934) exhibit more than 50% inhibition of the Cathepsin K activity at 0.1μM concentration and are considered to have a promising inhibitory effect against Cathepsin K. The comprehensive docking, MD simulation, and MM/PBSA investigations affirm the stable and effective interaction of these compounds with Cathepsin K to inhibit its function. Furthermore, the compounds RJC01981, KM08968 and SB01934 are represented to have promising anti-osteoporotic properties for the management of osteoporosis owing to their significantly well predicted ADMET properties.

The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review.

Cancer is one of the leading causes of death worldwide, making the search for alternatives for its control a critical issue. In this context, exploring alternatives from natural sources, such as certain vegetables containing a variety of secondary metabolites with beneficial effects on the body and that play a crucial role in the fight against cancer, is essential. Among the compounds with the greatest efficacy in controlling this disease, those with antioxidant activity, particularly phenolic com-pounds, stand out. A remarkable example of this group is protocatechuic acid (PCA), which has been the subject of various revealing research on its activities in different areas. These studies sustain that protocatechuic acid has anti-inflammatory, antimutagenic, antidiabetic, antiulcer, antiviral, antifibrogenic, antiallergic, neuroprotective, antibacterial, anticancer, antiosteoporotic, anti-aging, and analgesic properties, in addition to offering protection against metabolic syndrome and con-tributing to the preservation of hepatic, renal, and reproductive functionality. Therefore, this paper aims to review the biological activities of PCA, focusing on its anticancer potential and its in-volvement in the control of various molecular pathways involved in tumor development, sup-porting its option as a promising alternative for cancer treatment.

Icariin promotes bone marrow mesenchymal stem cells osteogenic differentiation via the mTOR/autophagy pathway to improve ketogenic diet-associated osteoporosis

BackgroundIcariin, a traditional Chinese medicine, has demonstrated anti-osteoporotic properties in ovariectomized mice. However, its effectiveness in preventing bone loss induced by ketogenic diet (KD), which mimics osteoporosis in human, remains unexplored. This study aims to investigate icariin’s impact on KD-induced bone loss in mice.MethodsThirty mice were divided into: sham, KD, and KD + icariin groups. Post a 12-week intervention, evaluation including bone microstructures, serum concentrations of tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (ALP), and femoral tissue expression levels of osteocalcin (OCN) and TRAP. The expression levels of mammalian target of rapamycin (mTOR), ALP, peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphorylated mTOR (p-mTOR), and the autophagy adaptor protein (p62) were also analyzed. Alizarin granule deposition and cellular ALP levels were measured following the induction of bone marrow mesenchymal stem cells (BMSCs) into osteogenesis.ResultsThe study found that KD significantly impaired BMSCs' osteogenic differentiation, leading to bone loss. Icariin notably increased bone mass, stimulated osteogenesis, and reduced cancellous bone loss. In the KD + icariin group, measures such as bone tissue density (TMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly higher than in the KD group. Additionally, bone trabecular separation (Tb.Sp) was markedly lower in the KD + icariin group. Moreover, icariin increased OCN and ALP levels while suppressing PPAR-γ, TRAP, p62, and p-mTOR. In cellular studies, icariin encouraged osteogenic development in BMSCs under KD conditions.ConclusionsIcariin effectively counteracts bone thinning and improves bone microstructure. Its mechanism likely involves stimulating BMSCs osteogenic differentiation and inhibiting bone resorption, potentially through mTOR downregulation. These findings suggest icariin's potential as an alternative treatment for KD-induced bone loss.

Effect and Mechanism of Curcumin on Bone Loss and Osteoporosis: A Systematic Review

Background: Curcumin has been used in various diseases due to its potent anti-oxidant and anti-inflammatory properties. Objective: This systematic review aims to investigate the effect and mechanism of curcumin on bone loss and osteoporosis. Methods: Those human cell line and clinical trial studies indexed in three databases, including PubMed, Institute for Scientific Information (ISI), and Scopus, were included in the review. Records with non-English language articles, full texts not retrieved, and studies that were not relevant to the purpose of our study were excluded. Finally, after evaluating all available records, 11 articles were included. Results: Curcumin induces antiosteoporotic properties by inhibiting the overproduction of reactive oxygen species (ROS) and free radical scavenging activity. Curcumin, through blocking nuclear factor kappa B (NF-κB) transmission to the nucleus, can suppress the production pathways of inflammatory cytokine production. Moreover, the biological mechanism of curcumin is a complex process associated with the modulation of transcription factors, protein kinases, and antiapoptotic proteins. Conclusion: The results of most clinical trials and human cell-based studies support the desirable impact of curcumin on bone loss and osteoporosis. Further clinical studies are needed to derive more reliable results about the prophylactic and therapeutic properties of curcumin on osteoporosis.

Integrating network pharmacology and experimental verification strategies to reveal the active ingredients and molecular mechanism of Tenghuang Jiangu Capsule against osteoporosis

Tenghuang Jiangu Capsule (THJGC) is a Chinese herbal formula used for the treatment of osteoporosis and osteoarthritis in China, but its mechanism for treating osteoporosis is not clear. The aim of this study was to investigate the therapeutic effect of THJGC on osteoporosis and its intrinsic mechanism through network pharmacology and experimental validation. Drugs and potential targets were obtained from several reliable databases through network pharmacology, and these targets were integrated and analyzed using bioinformatics and molecular docking strategies. Quercetin, lignans and kaempferol were identified as key components, and the key targets included Akt1, MAPKs, and CASP3. Subsequently, UPLC-MS/MS analysis confirmed the presence of components in THJGC for the treatment of osteoporosis. In addition, using ex vivo and in vivo models, it was confirmed that THJGC inhibited H2O2-induced ROS generation and apoptosis, and reduced OVX-induced bone loss in a mouse model of osteoporosis. Our data suggest that THJGC has antioxidant, bone formation-promoting, bone resorption-inhibiting, and MC3T3-E1 apoptosis-reducing effects, and thus has anti-osteoporotic properties. In conclusion, it may be a promising pharmacologic adjuvant treatment for osteoporosis.

The Health-Promoting Properties of Seaweeds: Clinical Evidence based on <i>Wakame</i> and <i>Kombu</i>

In this review, the botany, uses, bioactive metabolites, and health-promoting benefits of Undaria pinnatifida (wakame) and Saccharina japonica (kombu) are highlighted. Their clinical evidence is focused on clinical studies conducted in Japan and in other countries. These two species are brown seaweeds (Phaeophyta). In Japan, wakame and kombu seaweeds are popular food items consumed almost daily. Laboratory evidence shows that carotenoids (fucoxanthin and fucoxanthinol), polysaccharides (fucoidan) and sterols (fucosterol) are bioactive metabolites in wakame and kombu. Wakame displays antioxidant, anti-inflammatory, anticancer, antihypertensive, antidiabetic, antiviral, anticoagulant, antiosteoporotic, hepatoprotective, and antiobesity properties. Kombu possesses anticoagulant, antithrombotic, anticancer, hypolipidemic, hypoglycemic, antiobesity, antithrombotic, antiatherosclerosis, renal protective, vascular protective, antioxidant, antimicrobial, anti-inflammatory, immunomodulatory, gut biota regulatory, hypoglycemic, hypolipidemic, and neuroprotective activities. Clinical evidence on the effects of wakame intake was based on eight studies in Japan and eight studies in other countries. Clinical evidence on the effects of kombu intake was based on five studies in Japan. One case study on kombu dealt with severe alopecia areata. Some areas for future research on wakame and kombu are suggested. Information and data used in this review were from databases such as Google, Google Scholar, PubMed, PubMed Central, Science Direct, J-Stage, PubChem, China Academic Journals, and ClinicalTrials.gov.

Sustainable Bioactive Composite of Glehnia littoralis Extracts for Osteoblast Differentiation and Bone Formation

Different bone-related diseases are mostly caused by the disruption of bone formation and bone resorption, including osteoporosis. Traditional medicinal literature has reported the possible anti-osteoporotic properties of Glehnia littoralis. However, the chemical compounds in extracts that are responsible for bone metabolism are poorly understood. The present study aimed to explore and compare the coumarin-based compounds present in G. littoralis extracts, the antioxidant activities, and the anti-osteoporotic properties of different extracts of G. littoralis (leaf and stem, fruit, whole plant, and root extracts) on bone metabolism. This study analyzed G. littoralis extract effects on the proliferation and osteoblastic differentiation of MC3T3-E1 osteoblasts. Among the different tested samples, stem extracts had the highest scopoletin (53.0 mg/g), and umbelliferone (1.60 mg/g). The significantly (p < 0.05) highest amounts of imperatorin (31.9 mg/g) and phellopterin (2.3 mg/g), were observed in fruit and whole plant extracts, respectively. Furthermore, the results confirmed alkaline phosphatase activity, collagen synthesis, mineralization, osteocalcin content, and osterix and RUNX2 expression. G. littoralis extracts at concentrations greater than 20 µg/mL had particularly adverse effects on MC3T3-E1 cell viability and proliferation. Notably, cell proliferation was significantly elevated at lower G. littoralis concentrations. Comparatively, 0.5 µg/mL stem had a higher osteocalcin content. Of the four extract types, stem showed a higher collagen synthesis effect at concentrations of 0.5–5 µg/mL. Except for fruit extracts, G. littoralis extract treatment significantly elevated osterix gene expression. All G. littoralis extracts increased RUNX2 gene expression. The results described here indicate that G. littoralis ethanolic extracts can effectively prevent osteoporosis.

Occurrence, Chemistry and Synthesis of Various Novel Methods of Oxadiazole

Oxadiazoles are a kind of heterocyclic molecule that can be identified by their five-membered ring structure, two azo groups, and a single oxygen atom in their make-up. These characteristics allow them to be distinguished from other heterocyclic compounds. Because of these features, it is possible to differentiate them from several other heterocyclic compounds. They have the highest importance and relevance in the area of heterocyclic chemistry, which is also where they have the most value. They are of the biggest significance. Research is being conducted on it in substantial amounts due to the fact that it has the potential to function as a starting point for the synthesis of bioactive molecules that are beneficial to the body. This article provides a brief discussion of the physicochemical features of oxadiazole, including its spectra and a few examples of how it may be synthesised. The article can be found here. The pharmacological effects of oxadiazole derivatives were investigated by our team of researchers, and the findings indicated that these compounds had a number of positive benefits, including anti-inflammatory, anti-cancer, anti-fungal, anti-osteoporotic, and anti-microbial properties. In this piece, we will have a brief discussion on both synthetic and naturally occurring medications that include the oxadiazole ring in addition to the moiety. This talk will focus on pharmaceuticals that have been manufactured. The production of these compounds may take place in a laboratory, or they may be found occurring naturally in their natural environments.

Libanoridin Isolated from Corydalis heterocarpa Inhibits Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells.

Bone marrow adiposity is a complication in osteoporotic patients. It is a result of the imbalance between adipogenic and osteogenic differentiation of bone marrow cells. Phytochemicals can alleviate osteoporotic complications by hindering bone loss and decreasing bone marrow adiposity. Corydalis heterocarpa is a biennial halophyte with reported bioactivities, and it is a source of different coumarin derivatives. Libanoridin is a coumarin isolated from C. heterocarpa, and the effect of libanoridin on adipogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) was evaluated in the present study. Cells were induced to undergo adipogenesis, and their intracellular lipid accumulation and expression of adipogenic markers were observed under libanoridin treatment. Results showed that 10 μM libanoridin-treated adipocytes accumulated 44.94% less lipid compared to untreated adipocytes. In addition, mRNA levels of PPARγ, C/EBPα, and SREBP1c were dose-dependently suppressed with libanoridin treatment, whereas only protein levels of PPARγ were decreased in the presence of libanoridin. Fluorescence staining of adipocytes also revealed that cells treated with 10 μM libanoridin expressed less PPARγ compared to untreated adipocytes. Protein levels of perilipin and leptin, markers of mature adipocytes, were also suppressed in adipocytes treated with 10 μM libanoridin. Analysis of MAPK phosphorylation levels showed that treatment with libanoridin inhibited the activation of p38 and JNK MAPKs observed by decreased levels of phosphorylated p38 and JNK protein. It was suggested that libanoridin inhibited adipogenic differentiation of hBM-MSCs via suppressing MAPK-mediated PPARγ signaling. Future studies revealing the anti-adipogenic effects of libanoridin in vivo and elucidating its action mechanism will pave the way for libanoridin to be utilized as a nutraceutical with anti-osteoporotic properties.

Ameliorative Effect of Tocotrienols on Perimenopausal-Associated Osteoporosis-A Review.

Osteoporosis, or bone loss, is a disease that affects many women globally. As life expectancy increases, the risk of osteoporosis in women also increases, too, and this will create a burden on the healthcare and economic sectors of a country. Osteoporosis was once thought to be a disease that would occur only after menopause. However, many studies have shown that osteoporosis may develop even in the perimenopausal stage. Due to the erratic levels of estrogen and progesterone during the perimenopausal stage, studies suggest that women are exposed to the risk of developing osteoporosis even at this stage. The erratic hormonal changes result in the production of proinflammatory mediators and cause oxidative stress, which leads to the progressive loss of bone-building activities. Tocotrienols, members of vitamin E, have many health-promoting properties. Due to their powerful anti-oxidative and anti-inflammatory properties, tocotrienols have shown positive anti-osteoporotic properties in post-menopausal studies. Hence, we propose here that tocotrienols could also possibly alleviate perimenopausal osteoporosis by discussing in this review the connection between inflammatory mediators produced during perimenopause and the risk of osteoporosis. Tocotrienols could potentially be an anti-osteoporotic agent, but due to their low bioavailability, they have not been as effective as they could be. Several approaches have been evaluated to overcome this issue, as presented in this review. As the anti-osteoporotic effects of tocotrienols were mostly studied in post-menopausal models, we hope that this review could pave the way for more research to be done to evaluate their effect on peri-menopausal models so as to reduce the risk of osteoporosis from an earlier stage.

Beneficial health effects of cumin (Cuminum cyminum) seeds upon incorporation as a potential feed additive in livestock and poultry: A mini-review

Cumin (Cuminum cyminum Linn) is an annual plant of the family Umbelliferae, with its use dating back to ancient times when it was cultivated for its medicinal and culinary potential. Cumin seeds could contain a wide variety of phytochemicals, including alkaloids, coumarins, anthraquinones, flavonoids, glycosides, proteins, resins, saponins, tannins, and steroids. In particular, linoleic acid, one of the unsaturated fatty acids found in abundance in cumin oleoresin, is credited with promoting good health. Many of cumin's purported biological actions in livestock and poultry have been attributed to flavonoids such as apigenin, luteolin, and glycosides. Cumin has several healthful qualities, such as antibacterial, insecticidal, anti-inflammatory, analgesic, antioxidant, anticancer, anti-diabetic, anti-platelet aggregation, hypotensive, bronchodilatory, immunological, anti-amyloidogenic, and anti-osteoporotic properties. Cumin supplementation may improve milk production and reproductive function in dairy cows by altering the feeding pattern of bacteria in the rumen, encouraging the growth of beneficial microbes, or stimulating the secretion of certain digestive enzymes. Because of the low price of cumin seed, it could be concluded that its inclusion in the diet might be beneficial to the commercial poultry industry and reduce the overall cost of egg and meat production. In recent years a rise in cumin's popularity has been seen as a result of the herbal movement spearheaded by naturopaths, yoga gurus, advocates of alternative medicine, and manufacturers of feed additives. Animal nutritionists are exploring the use of cumin for its potential to boost growth, improve nutrient usage efficiency, and reduce greenhouse gas emissions. This mini-review discusses how cumin could be used as a feed ingredient to boost productivity and ensure healthy animal reproduction.

Therapeutic Effects of Live Lactobacillus plantarum GKD7 in a Rat Model of Knee Osteoarthritis

Osteoarthritis (OA) is a painful, progressive chronic inflammatory disease marked by cartilage destruction. Certain synovial inflammatory cytokines, such as IL-1β and TNF-α, promote OA inflammation and pain. Lactobacillus spp. is a well-known probiotic with anti-inflammatory, analgesic, antioxidant, and antiosteoporotic properties. This study evaluated the therapeutic effects of a live L. plantarum strain (GKD7) in the anterior cruciate ligament transection (ACLT)-induced OA rat model. The results show that oral administration of live L. plantarum GKD7 improved weight-bearing asymmetry after ACLT surgery. Moreover, micro-computed tomography images and histopathological analysis show that oral live L. plantarum GKD7 improved subchondral bone architecture, protected articular cartilage against ACLT-induced damage, and reduced synovial inflammation. L. plantarum GKD7 also reduced IL-1β and TNF-α production in OA cartilage and synovium. Thus, orally administered live L. plantarum GKD7 appears to effectively slow the progression of OA.

Antiproliferative Effects of Phytoestrogens Formononetin and Resveratrol Against Human Pulmonary Adenocarcinoma Cells A 549

Phytoestrogens are phytoalexins, plant secondary metabolites produced in response to microbial attacks and other forms of external stress stimuli. These compounds are devoid of the steroidal structure of endogenous estrogens but could bind with estrogen receptors with great affinity as they have structural similarity with endogenous/synthetic estrogens. Phytoestrogens are reported to possess several health benefits including cardio protective, antidiabetic, antioxidant and anti osteoporotic properties. Phytoestrogens like genistein, daidzein, and equol have been reported to possess excellent anti proliferative and anticancer properties. Formononetin, is a phytoestrogen, isoflavone widely present in red clover (Trifolium pratense) and resveratrol is a phytoestrogen which is widely present in red grapes (Vitis vinifera). The cardio protective property of red wine has been attributed to the presence of resveratrol. Although formononetin and resveratrol have been investigated extensively for several pharmacological properties, reports on their anti proliferative effects especially against human pulmonary carcinoma cell lines are very less. Hence the current study aims to understand the influence of these two compounds on the growth of human pulmonary adenocarcinoma cell line A 549. MTT assay, cytomorphology analysis by phase contrast microscopy, DNA topology assay and DPPH assay were few assays which were performed to understand the antiproliferative and antioxidant effects of these compounds. Results of the study indicated the potent antiproliferative effects of these compounds against human pulmonary carcinoma cell lines implicating that these compounds could be potential therapeutic molecules with multifaceted roles as anticancer agents, potent antioxidants and anti inflammatory agents.

Haematological Assessment of Methanolic Stem Extract of Cissus quadrangularisLinn. against Freund's Complete Adjuvant induced Female Albino Arthritic Rats

Rheumatoid arthritis is a chronic, inflammatory and autoimmune disorder. Rheumatoid arthritis is a joint destruction which occurs due to increased expression of cytokines and transcription factors. Cissus quadrangularis belongs to the Vitaceae family. The plant shows anti-osteoporotic, anti-inflammatory and anti-microbial properties. Soxhlet method was used for the extraction of the plant using methanol as a solvent. The anti-arthritic activity of methanolic extract of Cissus quadrangularis was evaluated by in vivo study. The present study assess the haematological parameters in female albino rats after the induction of Freund's Complete Adjuvant. Dexamethasone was used as the standard reference drug. The study showed varied changes in the haematology after the arthritic induction by 0.1 ml FCA which were analyzed before and afterthe treatment period. The inhibition of secondary inflammation in adjuvant arthritic rats by methanolic extract of Cissus quadrangularis was studied by haematological parameters. The total haemoglobin, total RBC, total WBC, ESR and RF values were assessed before initiation of the treatment and after for 28 days of the treatment. The results showed significant incline or decline in each parameter in the study period of 28 days. While their changes were rectified with the oral administration of methanolic extract of the plant at a dose of 250mg/kg. The methanolic extract boosted the levels of Hb, RBC and simultaneously reduced WBC, ESR levels along with the serological factor RF. The plant extract showed effective results in the haematological parameters, when compared to the standard reference drug Dexamethasone. The results from the study suggest that the plant has potential effect in curing arthritis.

Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications.

Nonalcoholic fatty liver disease (NAFLD) and osteoporosis are two highly prevalent metabolic diseases. Increasing experimental evidence supports a pathophysiological link between NAFLD and osteoporosis. A key feature could be chronic, low-grade inflammation, which characterizes NAFLD and possibly affects bone metabolism. In this context, several factors, including but not limited to receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, osteopontin and osteocalcin, may serve as mediators. In the clinical setting, most but not all epidemiological evidence indicates that NAFLD is associated with lower bone mineral density or osteoporosis in adults. Although an association between NAFLD and osteoporosis has not yet been established, and thus remains speculative, pharmacological considerations already exist. Some of the current and emerging pharmacological options for NAFLD have shown possible anti-osteoporotic properties (eg, vitamin E, obeticholic acid, semaglutide), while others (eg, pioglitazone, canagliflozin) have been associated with increased risk of fractures and may be avoided in patients with NAFLD and concomitant osteoporosis, especially those at high fracture risk. Conversely, some anti-osteoporotic medications (denosumab) might benefit NAFLD, while others (raloxifene) might adversely affect it and, consequently, may be avoided in patients with osteoporosis and NAFLD. If an association between NAFLD and osteoporosis is established, a medication that could target both diseases would be a great advancement. This review summarizes the main experimental and clinical evidence on the potential association between NAFLD and osteoporosis and focuses on treatment considerations derived from this potential association.

Protective effect of Du-Zhong-Wan against osteoporotic fracture by targeting the osteoblastogenesis and angiogenesis couple factor SLIT3

Ethnopharmacological relevanceDu-Zhong-Wan (DZW) is a traditional Chinese medicine (TCM) composed of Eucommia ulmoides Oliv. and Dipsacus asper Wall. ex C.B. Clarke in the ratio 1:1. Based on the TCM theory, DZW nourishes the kidney to strengthen the bones. The literature research revealed that DZW possesses anti-fatigue, anti-depressant, and anti-osteoporotic properties. However, the action and mechanism of DZW on osteoporotic fracture remains slightly unclear. Aim of the studyTo evaluate the pharmacological effect of DZW on ovariectomized mice with an open femoral fracture and reveal the underlying mechanism. Materials and methodsWe conducted ovariectomy for 5 weeks, followed by unilateral open transverse femoral fracture for another 3 weeks in C57BL/6 mice; during this process, DZW was administrated. The femur bone and vertebra tissues were collected and analyzed by micro-computed tomography, histomorphometry, mechanical strength testing, immunohistochemistry staining, and qRT-PCR analyses. In addition, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to determine the extent of osteoblastogenesis from bone marrow mesenchymal stem cells (BMSCs). Western blotting was performed to examine the protein expression. ResultsDZW treatment significantly improved the bone histomorphometric parameters in mice undergoing ovariectomy when combined with the femoral fracture, including an increase in the bone volume, trabecular number, and bone formation rate and a decrease in the bone erosion area. Simultaneously, DZW treatment histologically promoted fractured callus formation. Mechanical strength testing revealed significantly higher stiffness and an ultimate load after treatment with DZW. The angiogenesis of H-type vessels was enhanced by DZW, as evidenced by increased levels of CD31 and endomucin (EMCN), the H-type vessel endothelium markers, at the fractured endosteum and metaphysis regions. Relative to the osteoporotic fracture mice, the DZW treatment group showed an increased proangiogenic factor SLIT3 level. The increased level of SLIT3 was also recorded during the process of DZW-stimulated osteoblastogenesis from BMSCs. ConclusionsFor the first time, we demonstrated that DZW promoted osteoporotic fracture healing by enhancing osteoblastogenesis and angiogenesis of the H-type vessels. This enhanced combination of osteoblastogenesis and angiogenesis was possibly related to the production of proangiogenic factor SLIT3 induced by DZW.

In silico Target Class Prediction and Probabilities for Plant Derived Omega 3 Fatty Acid from Ethyl Acetate Fraction of Moringa oleifera Leaf Extract

Plant Derived Omega 3 Fatty Acid – α Linolenic Acid (ALA) a carboxylic acid with 18 carbon atoms, 3 cis double bonds. ALA obtained from plant based food source is converted into eicosa-pentaenoic acid (EPA) and docosa-hexaenoic acid (DHA). However, the rate of conversion is influenced by dose, gender, and health status. Further, intake of ALA significantly reduces the risk of sudden death among myocardial infarction patients consistent with induced antiarrhythmic effect. ALA is concomitant with cardiovascular-protective, anti-cancer, neuro-protective, anti-osteoporotic, anti-inflammatory, and anti-oxidative properties. ALA has anti-metabolic syndrome that regulates gut-micro-floral functionalities. Clinical trials indicate that ALA can be used in the management of multi-metabolic syndrome effects but in-depth target based ADMET studies are required to ascertain its clinical efficacy and market potential.
 Keywords: ADMET; Moringa oleifera; Secondary Metabolites; Natural Products (NPs); Bioactive Substances; Octadecatrienoic acid (ODA); Eicosa-Pentaenoic Acid (EPA); Docosa-Hexaenoic Acid (DHA); Plant Derived Omega 3 Fatty Acid (PDO3FA)

Orcinol Glucoside Improves Senile Osteoporosis through Attenuating Oxidative Stress and Autophagy of Osteoclast via Activating Nrf2/Keap1 and mTOR Signaling Pathway.

Oxidative stress and autophagy play essential roles in the development of senile osteoporosis which is characterized by disrupted osteoclastic bone resorption and osteoblastic bone formation. Orcinol glucoside (OG), a phenolic glycoside isolated from Curculigo orchioides Gaertn, possesses antiosteoporotic properties. This study examined the protective effects of OG on bone loss in SAMP6 mice and explored the underlying mechanisms. The osteoporotic SAMP6 mice were treated with OG oral administration. RAW264.7 cells were induced to differentiate into osteoclast by RANKL and H2O2 in vitro and received OG treatment. The results demonstrated that OG attenuated bone loss in SAMP6 mice and inhibited the formation and bone resorption activities of osteoclast and reduced levels of oxidative stress in bone tissue of SAMP6 mice and osteoclast. Furthermore, OG activated Nrf2/Keap1 signaling pathway and enhanced the phosphorylation of mTOR and p70S6K which are consequently suppressing autophagy. Of note, the effect of OG on Nrf2/Keap1 signaling was neutralized by the mTOR inhibitor rapamycin. Meanwhile, the inhibitory effect of OG on autophagy was reversed by the Nrf2 inhibitor ML385.Conclusively, OG attenuated bone loss by inhibiting formation, differentiation, and bone resorption activities of osteoclast. Regulation of Nrf2/Keap1 and mTOR signals is a possible mechanism by which OG suppressed oxidative and autophagy of osteoclasts. Thus, OG prevented senile osteoporosis through attenuating oxidative stress and autophagy of osteoclast via activating Nrf2/Keap1 and mTOR signaling pathway.

Astragalin Inhibits Insulin Resistance and Oxidative Stress in Palmitic Acid-Induced HEPG2 Cells

Insulin resistance is an element of metabolic syndrome, manifested as a decrease in glucose uptake, which often leads to a variety of complications, including type 2 diabetes. Astragalin is a natural flavonoid, isolated from traditional medicinal plants, such as Cuscuta chinensis, that has been shown to exhibit a variety of pharmacological activities with anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. However, the mechanism of astragalin on insulin resistance has not yet been elucidated. To this end, we examined the effect of astragalin on palmitic acid-induced insulin resistance in HepG2 cells. The effects of the co-incubation of PA and astragalin on the cell viability, superoxide dismutase, fat content, and markers of oxidative stress in HepG2 cells were measured. The results show that astragalin restored the cell viability, reduced oxidative stress, and insulin resistance in palmitic acid treated HepG2 cells. The protective effect of astragalin on palmitic acid-induced lipotoxicity in HepG2 cells was through inhibition of NF-was through inhibition of NF-κ and JNK signaling pathways.