Anti-inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma.

Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1ß (IL-1ß) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.

Aiouea padiformis extract exhibits anti-inflammatory effects by inhibiting the ATPase activity of NLRP3.

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.

Enhanced neuronal activity by suffruticosol A extracted from Paeonia lactiflora via partly BDNF signaling in scopolamine-induced memory-impaired mice.

Neurodegenerative diseases are explained by progressive defects of cognitive function and memory. These defects of cognition and memory dysfunction can be induced by the loss of brain-derived neurotrophic factors (BDNF) signaling. Paeonia lactiflora is a traditionally used medicinal herb in Asian countries and some beneficial effects have been reported, including anti-oxidative, anti-inflammatory, anti-cancer activity, and potential neuroprotective effects recently. In this study, we found that suffruticosol A is a major compound in seeds of Paeonia lactiflora. When treated in a SH-SY5 cell line for measuring cell viability and cell survival, suffruticosol A increased cell viability (at 20 µM) and recovered scopolamine-induced neurodegenerative characteristics in the cells. To further confirm its neural amelioration effects in the animals, suffruticosol A (4 or 15 ng, twice a week) was administered into the third ventricle beside the brain of C57BL/6 mice for one month then the scopolamine was intraperitoneally injected into these mice to induce impairments of cognition and memory before conducting behavioral experiments. Central administration of suffruticosol A into the brain restored the memory and cognition behaviors in mice that received the scopolamine. Consistently, the central treatments of suffruticosol A showed rescued cholinergic deficits and BDNF signaling in the hippocampus of mice. Finally, we measured the long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse to figure out the restoration of the synaptic mechanism of learning and memory. Bath application of suffruticosol A (40 µM) improved LTP impairment induced by scopolamine in hippocampal slices. In conclusion, the central administration of suffruticosol A ameliorated neuronal effects partly through elevated BDNF signaling.

Anti-Adipogenic Activity of Secondary Metabolites Isolated from Smilax sieboldii Miq. on 3T3-L1 Adipocytes.

Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical investigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1-19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at a concentration of 100 µM. Of these, compounds 1, 2, 4-9, 15, and 19 significantly reduced fat accumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19, showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 µM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation.

The central administration of vitisin a, extracted from Vitis vinifera, improves cognitive function and related signaling pathways in a scopolamine-induced dementia model.

Neurodegenerative disorders, such as Alzheimer's disease (AD), are characterized by cognitive function loss and progressive memory impairment. Vitis vinifera, which is consumed in the form of fruits and wines in various countries, contains several dietary stilbenoids that have beneficial effects on neuronal disorders related to cognitive impairment. However, few studies have investigated the hypothalamic effects of vitisin A, a resveratrol tetramer derived from V. vinifera stembark, on cognitive functions and related signaling pathways. In this study, we conducted in vitro, ex vivo, and in vivo experiments with multiple biochemical and molecular analyses to investigate its pharmaceutical effects on cognitive functions. Treatment with vitisin A increased cell viability and cell survival under H2O2-exposed conditions in a neuronal SH-SY5 cell line. Ex vivo experiments showed that vitisin A treatment restored the scopolamine-induced disruption of long-term potentiation (LTP) in the hippocampal CA3-CA1 synapse, indicating the restoration of synaptic mechanisms of learning and memory. Consistently, central administration of vitisin A ameliorated scopolamine-induced disruptions of cognitive and memory functions in C57BL/6 mice, as evidenced by Y-maze and passive avoidance tests. Further studies showed that vitisin A upregulates BDNF-CREB signaling in the hippocampus. Together, our findings suggest that vitisin A exhibits neuroprotective effects, at least partially, by upregulating BDNF-CREB signaling and LTP.

Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Phytochemical investigation on the aerial parts of Veratrum versicolor f. viride Nakai and their biological activities.

Veratrum spp. have traditionally been used in folk medicine to treat various pathologies. In this study, nine compounds, comprising one simple phenolic compound (1), three stilbenoids (2-4), and five flavonoids (5-9), were isolated from the aerial parts of Veratrum versicolor f. viride Nakai. The structures of these compounds were elucidated by spectroscopic analyses and comparison with reported data. Together, all reported compounds were isolated from V. versicolor f. viride for the first time in the study. Among them, two flavone aglycone tricetins (7 and 9) have never been isolated from the genus Veratrum or the family Melanthiaceae. The ethanol extract and isolated compounds were assessed for their inhibitory effects on elastase, tyrosinase, and melanin synthesis. Compounds 5 and 7 inhibited elastase (IC50: 292.25 ± 14.39 and 800.41 ± 5.86 µM, respectively), whereas compounds 2-5 inhibited tyrosinase with IC50 values in the range of 6.42 ~ 51.19 µM, respectively. In addition, compounds 3-6 and 8 exhibited dose-dependent inhibition (70.4% ~ 91.0%) of melanogenesis at a concentration of 100 µM.

Enhanced anti-wrinkle activity of adlay bran fermented with Lactobacillus brevis MJM60390.

OBJECTIVES: The aim of this study was to screen the lactic acid bacteria for fermentation of adlay bran and evaluate the anti-wrinkle effect of fermented and non-fermented adlay bran. METHODS: Adlay bran was fermented with candidate LAB and extracted with 70% ethanol. The extracts from LAB-fermented adlay bran and non-fermented adlay bran were evaluated for the anti-wrinkle effects by measuring the hyaluronan, collagen, and elastin production in cells using ELISA kit. The molecular anti-wrinkle mechanism was investigated by RT-qPCR. Furthermore, the antioxidant activity, total phenolic and flavonoid content were also determined. RESULTS: Among the tested LAB, Lactobacillus brevis MJM60390 was selected for the highest glycosidase activity. Both extracts from adlay bran (NFAB) and L. brevis MJM60390-fermented adlay bran (LBFAB) showed anti-wrinkle effect, and LBFAB showed higher activity. Compared with control, hyaluronan production was increased by 24.73% and 59.38%, collagen production was increased by -13.08% and 34.19%, and the elastin production was increased by 29.78% and 53.73% by NFAB and LBFAB treatment, respectively. Investigation on the mRNA expression showed that LBFAB upregulated the expression of Has 2 and Has 3 and downregulate HYAL1 and HYAL2. LBFAB also upregulated the mRNA expression of COL1A1, COL1A2, ELN and inhibited the expression of collagenase and elastase. However, not all of these genes were regulated by NFAB. Furthermore, the antioxidant activity was significantly increased after fermentation, and the content of the phenolic and flavonoid compounds also increased in the LBFAB. CONCLUSIONS: In this study, we demonstrated that fermentation of adlay bran with L. brevis MJM60390 enhanced the anti-wrinkle activity through increasing the hyaluronan synthesis in keratinocytes and improving collagen and elastin production in dermal fibroblasts.

Ribes fasciculatum Ameliorates High-Fat-Diet-Induced Obesity by Elevating Peripheral Thermogenic Signaling.

Ribes fasciculatum has been consumed as a food and as a traditional medicine for treating autoimmune diseases and aging in diverse countries. A previous study showed that a mixture of Ribes fasciculatum and Cornus officinalis prohibited adipocyte differentiation and lipid accumulation in preadipocytes and suppressed diet-induced obesity. Nevertheless, the mechanism of R. fasciculatum to regulate energy homeostasis solely through thermogenic signaling remains unclear. Thus, we investigated its effects on energy homeostasis using R. fasciculatum fed to C57BL/6 mice with a 45% high-fat diet. Chronic consumption of R. fasciculatum decreased the body weight of obese mice with increasing food intakes and improved metabolic-syndrome-related phenotypes. Therefore, we further tested its thermogenic effects. Cold chamber experiments and qPCR studies indicated that R. fasciculatum elevated thermogenic signaling pathways, demonstrated by increased body temperature and uncoupling protein 1 (UCP1) signaling in the white and brown adipose tissues. Afzelin is one major known compound derived from R. fasciculatum. Hence, the isolated compound afzelin was treated with preadipocytes and brown adipocytes for cell viability and luciferase assay, respectively, to further examine its thermogenic effect. The studies showed that the response of afzelin was responsible for cell viability and the increased UCP1. In conclusion, our data indicated that R. fasciculatum elevated peripheral thermogenic signaling through increased UCP1 via afzelin activation and ameliorated diet-induced obesity.

Lotus Seed Green Embryo Extract and a Purified Glycosyloxyflavone Constituent, Narcissoside, Activate TRPV1 Channels in Dorsal Root Ganglion Sensory Neurons.

Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbinis [PN]) green embryo extract. However, the specific bioactive components and associated molecular mechanisms remain largely unknown. This study aimed to identify the ion channel-activating mechanisms of PN extracts. Using fluorometric imaging and patch-clamp recordings, PN extracts were screened for calcium channel activation in dorsal root ganglion (DRG) neurons. The TRPV1 channels in DRG neurons were strongly activated by the PN extract (mean amplitude of 131 ± 45 pA at 200 µg/mL) and its purified glycosyloxyflavone narcissoside (401 ± 271 pA at 100 µM). Serial treatment with a 200 µg/mL PN extract in TRPV1-overexpressing HEK293T cells induced robust desensitization to 10 ± 10% of the initial current amplitude. Thus, we propose that the PN extract and narcissoside function as TRPV1 agonists. This new finding may advance our knowledge regarding the traditional and scientific functions of PN in human health and disease.

Galla rhois water extract inhibits enzymatic browning in apple juice partly by binding to and inactivating polyphenol oxidase.

Although Galla rhois has been used as a traditional medicine in Asian countries, there was no application of it in anti-browning food additives. Here, we tested whether Galla rhois inhibits apple juice browning. Apple juice browning was blocked at 250-1000 µg/ml of Galla rhois for 16 days but the effect of vitamin C did not last until a day. In vitro assays showed that the antioxidant capacity of Galla rhois was stronger than that of vitamin C. Further analysis by UPLC-MS/MS identified 17 phytochemicals containing gallotannin derivatives. Docking simulation and polyphenol oxidase activity assay indicate that the mechanisms underlying Galla rhois-mediated inhibition of the enzymatic browning include but are not limited to the combined effects of multiple compounds including galloylglucose- and gallate-derivates. Although marketability and long-term toxicity of Galla rhois should be tested, it may be applied as a food additive to elevate food quality.

Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system.

Sargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

The multi-functional roles of forkhead box protein O in skin aging and diseases.

Forkhead box, class O (FoxO) family members are multifunctional transcription factors that are involved in several metabolic processes, including energy metabolism, apoptosis, DNA repair, and oxidative stress. However, their roles in skin health have not been well-documented. Recent studies have indicated that FoxOs are important factors to control skin homeostasis and health. The activation or deactivation of some FoxO family members is closely related to melanogenesis, wound healing, acne, and melanoma. In this review, we have discussed the recent findings that demonstrate the relationship between FoxOs and skin health as well as the underlying mechanisms associated with their functions.

Central Administration of Ampelopsin A Isolated from Vitis vinifera Ameliorates Cognitive and Memory Function in a Scopolamine-Induced Dementia Model.

Neurodegenerative diseases are characterized by the progressive degeneration of the function of the central nervous system or peripheral nervous system and the decline of cognition and memory abilities. The dysfunctions of the cognitive and memory battery are closely related to inhibitions of neurotrophic factor (BDNF) and brain-derived cAMP response element-binding protein (CREB) to associate with the cholinergic system and long-term potentiation. Vitis vinifera, the common grapevine, is viewed as the important dietary source of stilbenoids, particularly the widely-studied monomeric resveratrol to be used as a natural compound with wide-ranging therapeutic benefits on neurodegenerative diseases. Here we found that ampelopsin A is a major compound in V. vinifera and it has neuroprotective effects on experimental animals. Bath application of ampelopsin A (10 ng/µL) restores the long-term potentiation (LTP) impairment induced by scopolamine (100 µM) in hippocampal CA3-CA1 synapses. Based on these results, we administered the ampelopsin A (10 ng/µL, three times a week) into the third ventricle of the brain in C57BL/6 mice for a month. Chronic administration of ampelopsin A into the brain ameliorated cognitive memory-behaviors in mice given scopolamine (0.8 mg/kg, i.p.). Studies of mice's hippocampi showed that the response of ampelopsin A was responsible for the restoration of the cholinergic deficits and molecular signal cascades via BDNF/CREB pathways. In conclusion, the central administration of ampelopsin A contributes to increasing neurocognitive and neuroprotective effects on intrinsic neuronal excitability and behaviors, partly through elevated BDNF/CREB-related signaling.

Antiosteoarthritic Effect of Morroniside in Chondrocyte Inflammation and Destabilization of Medial Meniscus-Induced Mouse Model.

Osteoarthritis (OA) is a common degenerative disease that results in joint inflammation as well as pain and stiffness. A previous study has reported that Cornus officinalis (CO) extract inhibits oxidant activities and oxidative stress in RAW 264.7 cells. In the present study, we isolated bioactive compound(s) by fractionating the CO extract to elucidate its antiosteoarthritic effects. A single bioactive component, morroniside, was identified as a potential candidate. The CO extract and morroniside exhibited antiosteoarthritic effects by downregulating factors associated with cartilage degradation, including cyclooxygenase-2 (Cox-2), matrix metalloproteinase 3 (Mmp-3), and matrix metalloproteinase 13 (Mmp-13), in interleukin-1 beta (IL-1ß)-induced chondrocytes. Furthermore, morroniside prevented prostaglandin E2 (PGE2) and collagenase secretion in IL-1ß-induced chondrocytes. In the destabilization of the medial meniscus (DMM)-induced mouse osteoarthritic model, morroniside administration attenuated cartilage destruction by decreasing expression of inflammatory mediators, such as Cox-2, Mmp3, and Mmp13, in the articular cartilage. Transverse microcomputed tomography analysis revealed that morroniside reduced DMM-induced sclerosis in the subchondral bone plate. These findings suggest that morroniside may be a potential protective bioactive compound against OA pathogenesis.

Central administration of afzelin extracted from Ribes fasciculatum improves cognitive and memory function in a mouse model of dementia.

Neurodegenerative disorders are characterized by the decline of cognitive function and the progressive loss of memory. The dysfunctions of the cognitive and memory system are closely related to the decreases in brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) signalings. Ribes fasciculatum, a medicinal plant grown in diverse countries, has been reported to pharmacological effects for autoimmune diseases and aging recently. Here we found that afzelin is a major compound in Ribes fasciculatum. To further examine its neuroprotective effect, the afzelin (100 ng/µl, three times a week) was administered into the third ventricle of the hypothalamus of C57BL/6 mice for one month and scopolamine was injected (i.p.) to these mice to impair cognition and memory before each behavior experiment. The electrophysiology to measure long-term potentiation and behavior tests for cognitive and memory functions were performed followed by investigating related molecular signaling pathways. Chronic administration of afzelin into the brain ameliorated synaptic plasticity and cognitive/memory behaviors in mice given scopolamine. Studies of mice's hippocampi revealed that the response of afzelin was accountable for the restoration of the cholinergic systems and molecular signal transduction via CREB-BDNF pathways. In conclusion, the central administration of afzelin leads to improved neurocognitive and neuroprotective effects on synaptic plasticity and behaviors partly through the increase in CREB-BDNF signaling.

Monoterpenoids from the Fruits of Amomum tsao-ko Have Inhibitory Effects on Nitric Oxide Production.

In our search for novel plant-derived inhibitors of nitric oxide (NO) with potential for treating inflammatory diseases, the phytochemicals of Amomum tsao-ko fruits were investigated, leading to the isolation of one bicyclic nonane (1), three menthene skeleton monoterpenoids (2-4), and two acyclic monoterpenoids (5 and 6). Their structures were identified using one- and two-dimensional nuclear magnetic resonance spectroscopy, and mass spectrometry. To the best of our knowledge, compounds 2-5 were obtained from the genus Amomum for the first time. All isolates were tested for their ability to inhibit lipopolysaccharide-stimulated NO overproduction in RAW264.7 cells. Compound 4 was found to inhibit NO production. Western blotting analysis indicated that active compound 4 can regulate inducible NO synthase expression. In addition, lipopolysaccharide-induced interleukin 1 beta and interleukin-6 overproduction was reduced in a concentration-dependent manner.

Diterpenoids and phenolic analogues from the roots of Aralia continentalis.

Two new compounds, including a nor-pimarane diterpenoid (continentanol, 1) and a phenolic derivative (aralianic acid, 2), along with the known diterpenoids (3-11), polyacetylenes (12-15), phenolic components (16-28), and phytosterols (29 and 30), were isolated from roots of Aralia continentalis. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1 D and 2 D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.[Formula: see text].

Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice.

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

Scopolin Attenuates Osteoporotic Bone Loss in Ovariectomized Mice.

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis.