d-Pinitol Improves Diabetic Sarcopenia by Regulation of the Gut Microbiome, Metabolome, and Proteome in STZ-Induced SAMP8 Mice.

d-Pinitol (DP) is primarily found in Vigna sinensis, which has been shown to have hypoglycemic and protective effects on target organs. However, the mechanism of DP in treating diabetic sarcopenia (DS) is still unclear. To explore the underlying mechanism of DS and the protective targets of DP by high-throughput analysis of 16S rRNA gene, metabolome, and the proteome. Streptozotocin-induced SAMP8 mice were intragastrically administrated DP (150 mg/kg) for 8 weeks. Fecal 16S rRNA gene sequencing and gastrocnemius muscle metabolomic and proteomic analyses were completed to investigate the gut-muscle axis interactions. DP significantly alleviated the muscle atrophy in diabetic mice. Dysfunction of the gut microbiota was observed in the DS mice. DP significantly reduced the Parabacteroides, Akkermansia, and Enterobacteriaceae, while it increased Lachnospiraceae_NK4A136. Metabolome and proteome revealed that 261 metabolites and 626 proteins were significantly changed in the gastrocnemius muscle of diabetic mice. Among these, DP treatment restored 44 metabolites and 17 proteins to normal levels. Functional signaling pathways of DP-treated diabetic mice included nucleotide metabolism, ß-alanine, histidine metabolism, ABC transporters, and the calcium signaling pathway. We systematically explored the molecular mechanism of DS and the protective effect of DP, providing new insights that may advance the treatment of sarcopenia.

Anti-inflammatory activity of d-pinitol possibly through inhibiting COX-2 enzyme: in vivo and in silico studies.

Introduction: D-pinitol, a naturally occurring inositol, has diverse biological activities like antioxidant, antimicrobial and anticancer activities. This study aimed to evaluate anti-inflammatory effect of d-pinitol in a chick model. Additionally, in silico studies were performed to evaluate the molecular interactions with cyclooxygenase-2 (COX-2). Methods: The tested groups received d-pinitol (12.5, 25, and 50 mg/kg) and the standard drugs celecoxib and ketoprofen (42 mg/kg) via oral gavage prior to formalin injection. Then, the number of licks was counted for the first 10 min, and the paw edema diameter was measured at 60, 90, and 120 min. Results and Discussion: The d-pinitol groups significantly (p < 0.05) reduced the number of paw licks and paw edema diameters, compared to negative control. When d-pinitol was combined with celecoxib, it reduced inflammatory parameters more effectively than the individual groups. The in silico study showed a promising binding capacity of d-pinitol with COX-2. Taken together, d-pinitol exerted anti-inflammatory effects in a dose-dependent manner, possibly through COX-2 interaction pathway.

The regulation of MFG-E8 on the mitophagy in diabetic sarcopenia via the HSPA1L-Parkin pathway and the effect of D-pinitol.

BACKGROUND: Diabetic sarcopenia is a disease-related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG-E8 affects mitophagy and the protective role of D-pinitol (DP) in diabetic sarcopenia. METHODS: In vivo, streptozotocin-induced diabetic SAM-R1 (STZ-R1) and SAM-P8 (STZ-P8) mice (16-week-old) were used, and STZ-P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D-galactose (DG) induced senescent C2C12 models were established and received DP, MFG-E8 plasmid (Mover)/siRNA (MsiRNA), or 3-MA/Torin-1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co-immunoprecipitation (CO-IP) were used for hunting the interacted proteins of MFG-E8. RESULTS: In vivo, sarcopenia, mitophagy deficiency, and up-regulated MFG-E8 were confirmed in the STZ-P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ-P8 vs. STZ-P8; all P < 0.01), such as increased lean mass (8.47 ± 0.81 g vs. 7.08 ± 1.64 g), grip strength (208.62 ± 39.45 g vs. 160.87 ± 26.95 g), rotarod tests (109.7 ± 11.81 s vs. 59.3 ± 20.97 s), muscle cross-sectional area (CSA) (1912.17 ± 535.61 µm2 vs. 1557.19 ± 588.38 µm2), autophagosomes (0.07 ± 0.02 per µm2 vs. 0.02 ± 0.01 per µm2), and cytolysosome (0.07 ± 0.03 per µm2 vs. 0.03 ± 0.01 per µm2). DP down-regulated MFG-E8 in both serum (DP + STZ-P8: 253.19 ± 34.75 pg/mL vs. STZ-P8: 404.69 ± 78.97 pg/mL; P < 0.001) and gastrocnemius muscle (WB assay. DP + STZ-P8: 0.39 ± 0.04 vs. STZ-P8: 0.55 ± 0.08; P < 0.01). DP also up-regulated PINK1, Parkin and LC3B-II/I ratio, and down-regulated P62 in gastrocnemius muscles (all P < 0.01). In vitro, mitophagy deficiency and MFG-E8 up-regulation were confirmed in diabetic and senescent models (all P < 0.05). DP and MsiRNA down-regulated MFG-E8 and P62, and up-regulated PINK1, Parkin and LC3B-II/I ratio to promote mitophagy as Torin-1 does (all P < 0.05). HSPA1L was confirmed as an interacted protein of MFG-E8 in IP and CO-IP assay. Mover down-regulated the expression of Parkin via the HSPA1L-Parkin pathway, leading to mitophagy inhibition. MsiRNA up-regulated the expression of PINK1 via SGK1, FOXO1, and STAT3 phosphorylation pathways, leading to mitophagy stimulation. CONCLUSIONS: MFG-E8 is a crucial target protein of DP and plays a distinct role in mitophagy regulation. DP down-regulates the expression of MFG-E8, reduces mitophagy deficiency, and alleviates the symptoms of diabetic sarcopenia, which could be considered a novel therapeutic strategy for diabetic sarcopenia.

The First Comprehensive Chemical Profiling of Vachellia gummifera (Willd.) Kyal. & Boatwr., a Plant with Medicinal Value.

Vachellia gummifera (Willd.) Kyal. & Boatwr. is a medicinal plant endemic to Morocco that has no documented studies on its chemical composition. In this study, the chemical composition of the water/methanol (4 : 1) extracts of air-dried leaf and stem samples of Moroccan V. gummifera was determined using UHPLC-MS and NMR. In total, over 100 metabolites were identified in our study. Pinitol was the major compound in both the leaf and stem extracts, being significantly more abundant in the former. Asparagine and 3-hydroxyheteroendrin were the second most abundant compounds in the stem and leaf extracts, respectively, though both compounds were present in each tissue. The other compounds included flavonoids based on quercetin, and phenolic derivatives. Eucomic acid, only identified in the stems and was the major aromatic compound distinguishing the leaf and stem profiles. Quercetin 3-O-(6''-O-malonyl)-ß-D-glucopyranoside was identified as the major flavonoid in the leaves but was also present in the stems. Other malonylated derivatives that were all flavonol glycosides based on myricetin, kaempferol, and isorhamnetin in addition to quercetin were also identified. This is the first report of eucomic acid and malonylated compounds in Vachellia species. This report provides valuable insights into the chemotaxonomic significance of the Vachellia genus.

D-Pinitol mitigates post-traumatic stress disorder-like behaviors induced by single prolonged stress in mice through mineralocorticoid receptor antagonism.

Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Current treatments for PTSD, typically serotonin reuptake inhibitors, have limited effectiveness for patients and often cause serious adverse effects. Therefore, a novel class of treatment with better pharmacological profile is necessary. D-Pinitol has been reported to be effective for depression and anxiety disorders, but there are no reports associated with PTSD. In the present study, we investigated the effects of D-pinitol in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of D-pinitol on emotional and cognitive impairments in the SPS mouse model. We also investigated the effects of D-pinitol on fear memory formation. Mineralocorticoid receptor transactivation assay, Western blot, and quantitative PCR were employed to investigate how D-pinitol exerts its pharmacological activities. D-Pinitol ameliorated PTSD-like behaviors in a SPS mouse model. D-Pinitol also normalized the increased mRNA expression levels and protein levels of the mineralocorticoid receptor in the amygdala. A mineralocorticoid receptor agonist reversed the effects of D-pinitol on fear extinction and recall, and the antagonistic property of D-pinitol against the mineralocorticoid receptor was confirmed in vitro. Our findings suggest that D-pinitol could serve as a potential therapeutic agent for PTSD due to its antagonistic effect on the mineralocorticoid receptor.

Changes in primary metabolite content may affect thrips feeding preference in soybean crops.

Past research has characterized the induction of plant defenses in response to chewing insect damage. However, little is known about plant responses to piercing-sucking insects that feed on plant cell-contents like thrips (Caliothrips phaseoli). In this study, we used NMR spectroscopy to measure metabolite changes in response to six days of thrips damage from two field-grown soybean cultivars (cv.), known for their different susceptibility to Caliothrips phaseoli. We observed that thrips damage reduces sucrose concentration in both cultivars, while pinitol, the most abundant leaf soluble carbohydrate, is induced in cv. Charata but not in cv. Williams. Thrips did not show preference for leaves where sucrose or pinitol were externally added, at tested concentration. In addition, we also noted that cv. Charata was less naturally colonized and contained higher levels of trigonelline, tyrosine as well as several compounds that we have not yet identified. We have established that preference-feeding clues are not dependent on the plants major soluble carbohydrates but may depend on other types of compounds or leaf physical characteristics.

D-pinitol alleviates diabetic cardiomyopathy by inhibiting the optineurin-mediated endoplasmic reticulum stress and glycophagy signaling pathway.

Diabetic cardiomyopathy (DCM) is an important complication resulting in heart failure and death of diabetic patients. However, there is no effective drug for treatments. This study investigated the effect of D-pinitol (DP) on cardiac injury using diabetic mice and glycosylation injury of cardiomyocytes and its molecular mechanisms. We established the streptozotocin-induced SAMR1 and SAMP8 mice and DP (150 mg/kg/day) intragastrically and advanced glycation end-products (AGEs)-induced H9C2 cells. H9C2 cells were transfected with optineurin (OPTN) siRNA and overexpression plasmids. The metabolic disorder indices, cardiac dysfunction, histopathology, immunofluorescence, western blot, and immunoprecipitation were investigated. Our results showed that DP reduced the blood glucose and AGEs, and increased the expression of heart OPTN in diabetic mice and H9C2 cells, thereby inhibiting the endoplasmic reticulum stress (GRP78, CHOP) and glycophagy (STBD1, GABARAPL1), and alleviating the myocardial apoptosis and fibrosis of DCM. The expression of filamin A as an interaction protein of OPTN downregulated by AGEs decreased OPTN abundance. Moreover, OPTN siRNA increased the expression of GRP78, CHOP, STBD1, and GABARAPL1 and inhibited the expression of GAA via GSK3ß phosphorylation and FoxO1. DP may be helpful to treat the onset of DCM. Targeting OPTN with DP could be translated into clinical application in the fighting against DCM.

D-Pinitol improves cognitive dysfunction and neuronal damage induced by isoproterenol via modulation of NF-κB/BDNF/GFAP signaling in Swiss albino mice.

Objectives: Neurological disorders are the world's most distressing problem. The adverse effects of current medications continue to compel scientists to seek safer, more effective, and economically affordable alternatives. In this vein, we explored the effect of D-Pinitol on isoproterenol-induced neurotoxicity in mice. Materials and Methods: Forty-two mice were randomly distributed into 7 groups each having 6 animals. Group I; received saline. Group II; received isoproterenol (ISO) 15 mg/kg/day, s.c. for 20 days. Group III, IV; received 50 and 100 mg/kg/day/oral of D-Pinitol, respectively along with ISO for 20 days. Group V; received D-Pinitol 100 mg/kg/day/oral for 20 days. Group VI; received propranolol 20 mg/kg/day/oral and ISO for 20 days. Group VII; received propranolol 20 mg/kg/day/oral for 20 days. On the 21st day after behavioral tests, blood was collected and mice were sacrificed for various biochemical, histopathological, and immunohistochemical analyses. Results: Chronic administration of isoproterenol caused neurotoxicity, cognitive dysfunction, and histopathological changes in the brain as evidenced by increase in GFAP, oxidative stress (via SOD, CAT, TBARS, and GSH), neuroinflammation (NF-kB, TNF-α, IL-6, and IL-10), and decrease in AchE and BDNF. Co-administration of D-Pinitol (100 mg/kg) significantly prevented these pathological alterations. The cognitive improvement was also observed through the forced swim test, elevated plus maze test, and rotarod test. Conclusion: Our findings on D-Pinitol thus clearly established its neuroprotective role in ISO-induced neurodegeneration in Swiss albino mice.

The Anti-Diabetic Pinitol Improves Damaged Fibroblasts.

Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known. Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVA-induced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-ß signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice.

Purpose: Diabetes can cause hippocampal damage and lead to cognitive impairment. Diabetic cognitive impairment (DCI) is a chronic complication of diabetes associated with a high disability rate; however, its pathogenesis and therapeutic targets are unclear. We aimed to explore the mechanism of hippocampal damage during diabetes and evaluate the potential role of D-pinitol (DP) in protecting hippocampal tissue and improving cognitive dysfunction. Methods: DP (150 mg/kg/day) was administered intragastrically to streptozocin-induced aging-accelerated mice for 8 weeks. Hippocampal tissues were examined using tandem mass tag (TMT)-based proteomics and liquid chromatography-mass spectrometry (LC-MS)/MS-based non-targeted metabolomic analysis. Differentially expressed proteins (DEPs) and differentially regulated metabolites (DRMs) were screened for further analysis, and some DEPs were verified using western blotting. Results: Our results showed that 329 proteins had significantly altered hippocampal expression in untreated diabetic mice (DM), which was restored to normal after DP treatment in 72 cases. In total, 207 DRMs were identified in the DM group, and the expression of 32 DRMs was restored to normal post-DP treatment. These proteins and metabolites are involved in metabolic pathways (purine metabolism, arginine and proline metabolism, and histidine metabolism), actin cytoskeleton regulation, oxidative phosphorylation, and Rap1-mediated signaling. Conclusions: Our study may help to better understand the mechanism of diabetic hippocampal damage and cognitive impairment and suggest a potential therapeutic target.

D-Pinitol attenuates postmenopausal symptoms in ovariectomized mice.

AIMS: Menopause is a natural process in women that can lead to post-menopausal syndrome with symptoms such as hot flushes, weight gain, anxiety, cognitive decline, and depression. Hormonal replacement therapy is commonly prescribed. However, it has serious adverse effects. Herbal medicinal products and isoflavones are used as alternatives. D-Pinitol found in Pinaceae and Fabaceae families has anti-inflammatory and antioxidant effects. However, it has not received as much attention as isoflavones. In this study, we investigated whether D-pinitol could alleviate post-menopausal symptoms using an ovariectomized (OVX) mouse model. MAIN METHODS: Female ICR mice were divided into six groups: sham (vehicle), OVX (vehicle), OVX + D-pinitol (10, 30, 100 mg/kg, p.o.), and OVX + estradiol (0.5 mg/kg, s.c.). Treatment with vehicle, D-pinitol, and estradiol began at seven weeks post ovariectomy. We employed several behavioral tests, hot-flush test, and Western blot analysis. KEY FINDINGS: We found that D-pinitol treatment (30, 100 mg/kg, p.o.) reversed cognitive dysfunction in OVX mice (novel object recognition and Y-maze test). Additionally, D-pinitol alleviated anxiety-like behaviors (elevated plus-maze) and reversed depressive-like behaviors (splash test, tail suspension test). It also normalized increased basal tail skin temperature in OVX mice. Moreover, D-pinitol administration reversed decreased expression of ERß and synaptophysin and phosphorylation of ERK and PI3K-Akt-GSK-3ß induced by OVX in the hippocampus and prefrontal cortex. SIGNIFICANCE: These findings indicate that D-pinitol might be a promising candidate for treating post-menopausal symptoms by increasing ERß and synaptophysin expression levels and activation of ERK or PI3K-Akt-GSK-3ß signaling pathway, at least in part.

Effect of D-pinitol on MK-801-induced schizophrenia-like behaviors in mice.

Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.

D-pinitol ameliorated H2O2-induced oxidative damage in PC12 cells and prolonged the lifespan by IIS pathway in Caenorhabditis elegans.

D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed H2O2-induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans, DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aß in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16, skn-1, hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3, ctl-1, ctl-2, gst-4, hsp-16.1, and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future.

Preventing Adipogenesis and Preserving Mitochondria and GLUT-4 Functions by Extracts and Isolated Compounds of Australian Acacia saligna.

Acacia saligna's secondary metabolites show promise in treating type 2 diabetes mellitus and its related conditions. We previously discovered that methanolic extracts, isolated flavonoids, and cyclitols effectively preserve mitochondria in 3T3-L1 adipocytes. In this current work, quantification of lipid droplet levels with Oil Red O assay showed a noticeable decrease in lipogenesis in 3T3-L1 cells. Methanolic leaf and bark extracts and isolated compounds, (-)-epicatechin 6 and myricitrin 8, reduced cellular lipid levels by 21.15% to 25.28%, respectively. mRNA levels of key regulators of mitochondrial biogenesis, such as adiponectin, PGC-1α, and mtTFA, were increased. Methanolic flower extract (FL-MeOH) and its chemical components, naringenin 1 and D-(+)-pinitol 5a, increased these gene levels from 10% to 29% at the higher dose. Our study found that FL-MeOH slightly reduced pro-inflammatory cytokines TNF-α and IL-6, attributed to two phytochemicals, naringenin-7-O-α-L-arabinofuranoside 2 and D-(+)-pinitol 5a. Western blot analysis also showed that adipocytes treated with MeOH extracts had higher GLUT-4 expression levels than untreated adipocytes. Overall, A. saligna extracts and their isolated compounds demonstrated anti-lipogenesis activity during 3T3-L1 cell differentiation, modulation of transcriptional levels of adiponectin, PGC-1α, and mtTFA, reducing TNF-α and IL-6 mRNA levels, promoting mitochondrial biogenesis, and enhancing GLUT-4 expression.

D-Pinitol Content and Antioxidant and Antidiabetic Activities of Five Bougainvillea spectabilis Willd. Cultivars.

Diabetes mellitus is a major challenge for global health, and Bougainvillea spectabilis Willd. (B. spectabilis) is a widely used herbal remedy with diverse cultivars traditionally used for diabetes treatment. However, the comparative efficacy of these cultivars remains ambiguous. This study aimed to evaluate the D-pinitol content and DPPH radical-scavenging activity of methanolic leaves extracts of five B. spectabilis cultivars. Furthermore, the effects of these cultivars on various parameters, including blood glucose levels, oxidative stress markers, inflammatory cytokines, lipid profiles, liver enzymes, renal function markers, and histopathological changes, were assessed in STZ-induced diabetic rats after one month of oral daily treatment. All tested cultivars demonstrated significant improvements in the measured parameters, albeit to varying extents. Notably, the LOE cultivar, distinguished by its orange bracts, exhibited the highest efficacy, surpassing the effectiveness of glibenclamide, an antidiabetic medication, and displayed the highest concentration of D-pinitol. These findings underscore the importance of carefully selecting the appropriate B. spectabilis cultivar to maximize the antidiabetic efficacy, with a particular emphasis on the correlation between antidiabetic activity and D-pinitol concentrations.

Cyclitols: From Basic Understanding to Their Association with Neurodegeneration.

One of the most common cyclitols found in eukaryotic cells-Myo-inositol (MI) and its derivatives play a key role in many cellular processes such as ion channel physiology, signal transduction, phosphate storage, cell wall formation, membrane biogenesis and osmoregulation. The aim of this paper is to characterize the possibility of neurodegenerative disorders treatment using MI and the research of other therapeutic methods linked to MI's derivatives. Based on the reviewed literature the researchers focus on the most common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Spinocerebellar ataxias, but there are also works describing other seldom encountered diseases. The use of MI, d-pinitol and other methods altering MI's metabolism, although research on this topic has been conducted for years, still needs much closer examination. The dietary supplementation of MI shows a promising effect on the treatment of neurodegenerative disorders and can be of great help in alleviating the accompanying depressive symptoms.

D-Pinitol Ameliorated Osteoporosis via Elevating D-chiro-Inositol Level in Ovariectomized Mice.

A natural sugar alcohol, D-pinitol, has been reported to be a potential compound for osteoporosis treatment via inhibiting osteoclastgenesis. However, research on the effects of pinitol on osteoporosis in vivo is still limited. The present study investigated the protective effects of pinitol on ovariectomized mice and attempted to elucidate this mechanism in vivo. Four-week-old female ovariectomized ICR mice were employed as a postmenopausal osteoporosis model and treated with pinitol or estradiol (E2) for 7 wk. Thereafter, serum calcium content, phosphorus content, tartrate-resistant acid phosphatase (TRAcP) and bone-specific alkaline phosphatase activity (BALP) were measured. Bilateral femurs were isolated, and bone marrow protein was collected through centrifuge. Dry femurs were weighed, while femur length, cellular bones, and bone mineral content were measured. D-chiro-Inositol (DCI) and myo-inositol (MI) content in serum and bone marrow was measured by GC-MS. At the end of experiment, the serum BALP and TRAcP activities of the OVX mice were suppressed significantly by treatment with either pinitol or E2. Femur weight, cellular bone rate, Ca and P content were improved by pinitol or E2. The DCI content of the serum of OVX decreased significantly, although it recovered to some extent after pinitol treatment. Pinitol significantly increased the ratio of DCI to MI in serum or bone marrow protein in the observed OVX mice. Besides, pinitol had no significant effects on osteoblast viability and differentiation. The present results showed that continuous pinitol intake exerts potent anti-osteoporosis activity via elevating DCI content in serum and bone marrow in OVX mice.

Anti-Alzheimer Potential of a New (+)-Pinitol Glycoside Isolated from Tamarindus indica Pulp: In Vivo and In Silico Evaluations.

Tamarindus indica Linn (tamarind, F. Leguminosae) is one of the most widely consumed edible fruits in the world. Phytochemical investigation of tamarind pulp n-butanol fraction yielded one new (+)-pinitol glycoside compound 1 (25% w/w), and 1D, 2D NMR, and HRESIMS investigation were used to confirm the new compound's structure. (+)-Pinitol glycoside showed anti-Alzheimer potential that was confirmed in prophylactic and treatment groups by decreasing time for the T-maze test; decreased TAO, brain and serum AChE, MDA, tau protein levels, and ß amyloid peptide protein levels; and increasing GPX, SOD levels, and in vivo regression of the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model. The reported molecular targets for human Alzheimer's disease were then used in a network pharmacology investigation to examine their complex interactions and identify the key targets in the disease pathogenesis. An in silico-based analysis (molecular docking, binding free energy calculation (ΔGBinding), and molecular dynamics simulation) was performed to identify the potential targets for compound 1. The findings of this study may lead to the development of dietary supplements for the treatment of Alzheimer's disease.

The Metabolic Profile of Young, Watered Chickpea Plants Can Be Used as a Biomarker to Predict Seed Number under Terminal Drought.

Chickpea is the second-most-cultivated legume globally, with India and Australia being the two largest producers. In both of these locations, the crop is sown on residual summer soil moisture and left to grow on progressively depleting water content, finally maturing under terminal drought conditions. The metabolic profile of plants is commonly, correlatively associated with performance or stress responses, e.g., the accumulation of osmoprotective metabolites during cold stress. In animals and humans, metabolites are also prognostically used to predict the likelihood of an event (usually a disease) before it occurs, e.g., blood cholesterol and heart disease. We sought to discover metabolic biomarkers in chickpea that could be used to predict grain yield traits under terminal drought, from the leaf tissue of young, watered, healthy plants. The metabolic profile (GC-MS and enzyme assays) of field-grown chickpea leaves was analysed over two growing seasons, and then predictive modelling was applied to associate the most strongly correlated metabolites with the final seed number plant-1. Pinitol (negatively), sucrose (negatively) and GABA (positively) were significantly correlated with seed number in both years of study. The feature selection algorithm of the model selected a larger range of metabolites including carbohydrates, sugar alcohols and GABA. The correlation between the predicted seed number and actual seed number was R2 adj = 0.62, demonstrating that the metabolic profile could be used to predict a complex trait with a high degree of accuracy. A previously unknown association between D-pinitol and hundred-kernel weight was also discovered and may provide a single metabolic marker with which to predict large seeded chickpea varieties from new crosses. The use of metabolic biomarkers could be used by breeders to identify superior-performing genotypes before maturity is reached.

D-Pinitol Improved Glucose Metabolism and Inhibited Bone Loss in Mice with Diabetic Osteoporosis.

Diabetic osteoporosis (DO) has been increasingly recognized as an important complication of diabetes. D-pinitol, a natural compound found in various legumes, is known for its anti-diabetic function, but its effect on DO has not been investigated. Two doses of pinitol (50 and 100 mg/kg Bw/d) were administered orally to experimentally induce the DO mouse model for 5 weeks. The results indicated that pinitol suppressed fasting blood glucose levels and tended to enhance impaired pancreatic function. Pinitol also suppressed serum bone turnover biomarkers, and improved dry femur weight, cancellous bone rate, and bone mineral content in the DO mice. Based on the inositol quantification using GC-MS in serum, liver, kidney, and bone marrow, the pinitol treatment significantly recovered the depleted D-chiro-inositol (DCI) content or the decreased the ratio of DCI to myo-inositol caused by DO. In short, our results suggested that pinitol improved glucose metabolism and inhibited bone loss in DO mice via elevating the DCI levels in tissues.