Liquiritin apioside alleviates colonic inflammation and accompanying depression-like symptoms in colitis by gut metabolites and the balance of Th17/Treg.

BACKGROUND: Inflammatory bowel disease (IBD) is a significant global health concern that can lead to depression in affected patients. Liquiritin apioside (LA) possesses anti-oxidative and anti-inflammatory properties. However, its anti-inflammatory mechanism in IBD has not been extensively studied. PURPOSE: This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice. METHODS: To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry. RESULTS: Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites. CONCLUSION: These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.

Morin exhibits a neuroprotective effect in MPTP-induced Parkinson's disease model via TFEB/AMPK-mediated mitophagy.

BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. Mitophagy has been implicated in PD etiology for decades and its pharmacological activation is recognized as a promising treatment strategy for PD. For mitophagy initiation, low mitochondrial membrane potential (ΔΨm) is essential. We identified a natural compound morin that could induce mitophagy without affecting ΔΨm. Morin is a flavonoid that can be isolated from fruits like mulberry. PURPOSE: To reveal the effect of morin on the PD mice model and their potential underlying molecular mechanism. METHODS: Mitophagy process induced by morin in N2a cells meditation were measured using flow cytometry and immunofluorescence. JC-1 fluorescence dye used to detect the mitochondrial membrane potential (ΔΨm). The TFEB nuclear translocation were examined by immunofluorescence staining and western blot assay. The PD mice model was induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intraperitoneal administration. RESULTS: We found that morin also promoted nuclear translocation of the mitophagy regulator TFEB and activated the AMPK-ULK1 pathway. In MPTP-induced PD in vivo models, morin protected DA neurons from MPTP neurotoxicity and ameliorated behavioral deficit. CONCLUSION: Although morin was previously reported to be neuroprotective in PD, the detailed molecular mechanisms remain to be elucidated. For the first time, we report morin served as a novel and safe mitophagy enhancer underlying AMPK-ULK1 pathway and exhibited anti-Parkinsonian effects indicating its potential as a clinical drug for PD treatment.

Feruloylated oligosaccharides ameliorate MPTP-induced neurotoxicity in mice by activating ERK/CREB/BDNF/TrkB signalling pathway.

BACKGROUND: Feruloylated oligosaccharides (FOs) are natural esterification products of ferulic acid and oligosaccharides. STUDY DESIGN: In this study, we examined whether FOs contribute to the ensured survival of nigrostriatal dopamine neurons and inhibition of neuroinflammation in Parkinson's disease (PD). METHODS: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) was injected intraperitoneally into mice to establish a Parkinson's disease (PD) mouse model. FOs (15 and 30 mg/kg) were orally administered daily to the MPTP-treated mice. The rotarod test, balance beam test, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), and western blot analyses were performed to examine the neuroprotective effects of FOs on MPTP-treated mice. RESULTS: Our study indicated that FOs increased the survival of dopamine neurons in the substantia nigra pars compacta (SNc) of the MPTP-treated mice. The neuroprotective effects of FOs were accompanied by inhibited glial activation and reduced inflammatory cytokine production. The mechanistic experiments revealed that the neuroprotective effects of FOs might be mediated through the activation of the ERK/CREB/BDNF/TrkB signalling pathway. CONCLUSION: This study provides new insights into the mechanism underlying the anti-neuroinflammatory effect of phytochemicals and may facilitate the development of dietary supplements for PD patients. Our results indicate that FOs can be used as potential modulators for the prevention and treatment of PD.

Recyclable Endogenous H2 S Activation of Self-Assembled Nanoprobe with Controllable Biodegradation for Synergistically Enhanced Colon Cancer-Specific Therapy.

Excessive production of hydrogen sulfide (H2 S) plays a crucial role in the progress of colon cancer. Construction of tumor-specific H2 S-activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2 S triggered Co-doped polyoxometalate (POM-Co) cluster with self-adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2 S/glutathione (GSH) is designed for synergistic enhanced tumor-specific photothermal and chemodynamic therapy. The designed POM-Co nanocluster holds H2 S responsive "turn-on" photothermal property in colon cancer via self-assembling to form large-sized POM-CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM-CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)-catalyzed •OH production and Russell mechanism-enabled 1 O2 generation with GSH consumption, respectively. More importantly, the degraded POM-CoS is reactivated by endogenous H2 S for recyclable and sustainable consumption of H2 S and GSH, resulting in tumor-specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment-driven nanoprobes with controllable biodegradation for precise and sustainable anti-tumor therapy.

Antidepressant Active Ingredients From Chinese Traditional Herb Panax Notoginseng: A Pharmacological Mechanism Review.

Depression is one of the most common mental illnesses in the world and is highly disabling, lethal, and seriously endangers social stability. The side effects of clinical drugs used to treat depression are obvious, and the onset time is longer. Therefore, there is a great demand for antidepressant drugs with better curative effects, fewer side effects, and shorter onset time. Panax notoginseng, a Chinese herbal medication, has been used to treat depression for thousands of years and shown to have a therapeutic effect on depression. This review surveyed PubMed's most recent 20 years of research on Panax notoginseng's use for treating depression. We mainly highlight animal model research and outlined the pathways influenced by medicines. We provide a narrative review of recent empirical evidence of the anti-depressive effects of Panax Notoginseng and novel ideas for developing innovative clinical antidepressants with fewer side effects.

Polyphenols in edible herbal medicine: targeting gut-brain interactions in depression-associated neuroinflammation.

Supplementing with edible herbal medicine is an important strategy because of its role in nutrition. Many polyphenols, which are universal components in edible herbal medicines, have low bioavailability. Therefore, gut microbiota is a key determinant of polyphenol bioactivity. Polyphenols can alter the abundance of flora associated with neuroinflammation by reversing intestinal microbiota dysbiosis. Intestinal flora-mediated chemical modification of polyphenols can result in their conversion into active secondary metabolites. The current review summarizes the main edible medicines used in anti-depression and details the interactions between polyphenols and gut microbiota; in addition, it provides insights into the mechanisms underlying the possible suppression of neuroinflammation associated with depression, by polyphenols in edible herbal medicine. A better understanding of polyphenols with bioactivities that are crucial in edible herbal medicine may facilitate their use in the prevention and treatment of neuroinflammation associated with depression.

Chitosan-Gelatin-EGCG Nanoparticle-Meditated LncRNA TMEM44-AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5-FU Resistance in Gastric Cancer.

Chemoresistance is one of the leading causes of therapeutic failure in gastric cancer (GC) treatment. Recent studies have shown lncRNAs play pivotal roles in regulating GC chemoresistance. Nanocarriers delivery of small interfering RNAs (siRNAs) to silence cancer-related genes has become a novel approach to cancer treatment research. However, finding target genes and developing nanosystems capable of selectively delivering siRNAs for disease treatment remains a challenge. In this study, a novel lncRNA TMEM44-AS1 that is related to 5-FU resistance is identified. TMEM44-AS1 has the ability to bind to and sponge miR-2355-5p, resulting in the upregulated PPP1R13L expression and P53 pathway inhibition. Next, a new nanocarrier called chitosan-gelatin-EGCG (CGE) is developed, which has a higher gene silencing efficiency than lipo2000, to aid in the delivery of a si-TMEM44-AS1 can efficiently silence TMEM44-AS1 expression to synergistically reverse 5-FU resistance in GC, leading to a markedly enhanced 5-FU therapeutic effect in a xenograft mouse model of GC. These findings indicate that TMEM44-AS1 may estimate 5-FU therapy outcome among GC cases, and that systemic si-TMEM44-AS1 delivery combined with 5-FU therapy is significant in the treatment of patients with recurrent GC.

Xiaoyaosan inhibits neuronal apoptosis by regulating the miR-200/NR3C1 signaling in the prefrontal cortex of chronically stressed rats.

BACKGROUND: Depression is a prevalent emotion disorder which is thought to be due to neuronal structural alterations and/or functional impairment within specific brain regions. Several studies have shown that microRNAs are involved in the pathogenesis of depression. As a Chinese herbal formula, Xiaoyaosan (XYS) could have antidepressive effects, although the mechanisms associated with microRNAs are poorly understood. PURPOSE: In this study, we investigated whether inhibition of the miR-200a/b-3p/NR3C1 pathway in the prefrontal cortex is involved in the anti-neuronal apoptosis and anti-stress effects of XYS and then further delineated the underlying mechanism. METHODS: To evaluate the efficacy of XYS in relieving stress behaviors and altering the expression of miRNAs involved in the regulation of these behaviors in vivo, a chronic unpredictable mild stress (CUMS) rodent model and RNA-seq were performed. Primary cortical neurons were used to evaluate the molecular function of miR-200a/b-3p and detect the in vitro neuroprotective function of paeoniflorin, which is one of the main components of XYS. To investigate the function of miR-200a/b-3p in stress behaviors, stereotactic microinjection of AAV2/9-Syn-miR-200a/b-3p was performed to deliver the treatment to the rat mPFC. RESULTS: XYS reduced the anxiety and depression-like behaviors associated with chronic stress and reduced the expression of miR-200a/b-3p and neuronal apoptosis in the prefrontal cortex (PFC). The overexpression of miR-200a/b-3p in primary cortical neurons reduced the expression of the target gene NR3C1, increased the protein expression of cleaved caspase-3 and Bax, and decreased the anti-apoptotic protein Bcl-2. One of the active ingredients of XYS, paeoniflorin, can inhibit miR-200a/b-3p-mediated apoptosis of primary neurons and abnormal expression of apoptosis-related proteins. After overexpressing miR-200a/b-3p in vivo (vmPFC), the rats eventually showed significant anxiety-like behaviors similar to those caused by chronic stress. CONCLUSION: Our findings indicate that XYS can inhibit the CUMS-induced expression of miR-200a/b-3p, regulate miR-200a/b-3p/NR3C1 signaling in the PFC caused by chronic stress, and reduce neuronal apoptosis and stress-related behaviors.

Xiaoyaosan Improves Antibiotic-Induced Depressive-Like and Anxiety-Like Behavior in Mice Through Modulating the Gut Microbiota and Regulating the NLRP3 Inflammasome in the Colon.

Disturbance of the gut microbiota plays an essential role in mental disorders such as depression and anxiety. Xiaoyaosan, a traditional Chinese medicine formula, has a wide therapeutic spectrum and is used especially in the management of depression and anxiety. In this study, we used an antibiotic-induced microbiome-depleted (AIMD) mouse model to determine the possible relationship between imbalance of the intestinal flora and behavioral abnormalities in rodents. We explored the regulatory effect of Xiaoyaosan on the intestinal flora and attempted to elucidate the potential mechanism of behavioral improvement. We screened NLRP3, ASC, and CASPASE-1 as target genes based on the changes in gut microbiota and explored the effect of Xiaoyaosan on the colonic NLRP3 pathway. After Xiaoyaosan intervention, AIMD mice showed a change in body weight and an improvement in depressive and anxious behaviors. Moreover, the gut flora diversity was significantly improved. Xiaoyaosan increased the abundance of Lachnospiraceae in AIMD mice and decreased that of Bacteroidaceae, the main lipopolysaccharide (LPS)-producing bacteria, resulting in decreased levels of LPS in feces, blood, and colon tissue. Moreover, serum levels of the inflammatory factor, IL-1ß, and the levels of NLRP3, ASC, and CASPASE-1 mRNA and DNA in the colon were significantly reduced. Therefore, Xiaoyaosan may alleviate anxiety and depression by modulating the gut microbiota, correcting excessive LPS release, and inhibiting the immoderate activation of the NLRP3 inflammasome in the colon.

Current Prevention of COVID-19: Natural Products and Herbal Medicine.

Starting from December 2019, novel coronavirus disease 2019 (COVID-19) pandemic has caused tremendous economic loss and unprecedented health crisis across the globe. While the development of cure is at full speed, less attention and fewer effort have been spent on the prevention of this rapidly spreading respiratory infectious disease. Although so far, several vaccine candidates have advanced into clinical trials, limited data have been released regarding the vaccine efficacy and safety in human, not mention the long-term effectiveness of those vaccines remain as open question yet. Natural products and herbal medicines have been historically used for acute respiratory infection and generally show acceptable toxicity. The favorable stability for oral formulation and ease of scaling up manufacture make it ideal candidate for prophylactic. Hereby, we summarized the most recent advance in SARS-CoV-2 prevention including vaccine development as well as experimental prophylactics. Mainly, we reviewed the natural products showing inhibitory effect on human coronavirus, and discussed the herbal medicines lately used for COVID-19, especially focused on the herbal products already approved by regulatory agency with identifiable patent number. We demonstrated that to fill in the response gap between appropriate treatment and commercially available vaccine, repurposing natural products and herbal medicines as prophylactic will be a vigorous approach to stop or at least slow down SARS-CoV-2 transmission. In the interest of public health, this will lend health officials better control on the current pandemic.

Feruloylated oligosaccharides and ferulic acid alter gut microbiome to alleviate diabetic syndrome.

Gut microbiome has been proven to be involved in the development of type 2 diabetes (T2D). Additionally, increasing evidence showed that the composition of gut microbiome is highly associated with the outcome of T2D therapy. Previously we demonstrated that feruloylated oligosaccharides (FOs) and ferulic acid (FA) alleviated diabetic syndrome in rats, but the detailed mechanism has not been explored yet. In this study we strived to characterize how FOs and FA altered the gut microbiome and related metabolome in diabetic rats by using high-throughput sequencing of 16S rRNA and gas chromatography (GC). Our results showed that FOs reduced the abundance of Lactobacillus, Ruminococcus, Oscillibacter, and Desulfovibrio, but increased the abundance of Akkermansia, Phascolarctobacterium and Turicibacter. The structure of gut microbiome in FOs treated rats was similar with healthy rats rather than diabetic rats. Likewise, FA decreased the portion of Lactobacillus, Ruminococcus, but promoted the growth of Bacteroides, Blautia, Faecalibacterium, Parabacteroides and Phascolarctobacterium. Additionally, the short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), the main bacterial lipid metabolites in gut mediating host glucose metabolism, was dramatically elevated along with FOs and FA treatment. Our findings indicated that FOs and FA attenuated diabetic syndrome in rats most likely by modulating the composition and metabolism of gut microbiome. The study gives new insight into the mechanism underlying the anti-diabetes effect of functional foods as well as facilitates the development of dietary supplements for diabetic patients.

Quantifying Liver-Stomach Disharmony Pattern of Functional Dyspepsia Using Multidimensional Analysis Methods.

PURPOSE: This study aims to develop and validate a quantitative model for measuring severity of a typical traditional Chinese medicine (TCM) pattern for functional dyspepsia (FD) using multidimensional analysis methods including confirmatory factor analysis (CFA) and multidimensional item response theory (MIRT). METHODS: A scale and theoretical models were constructed according to the definition of pathogenesis about "liver-stomach disharmony" patterns of FD. With data collected from 502 patients in a cross-section study, the theoretical model was validated with CFA, and the related validity and reliability were evaluated in Amos 21.0. By the use of the MIRT paradigm, psychometric properties of the scale were estimated and evaluated for pattern quantification. RESULTS: A scale consisting of 12 items was constructed detecting three latent traits of the pattern. The theoretical model was evaluated to be with adequate consistency with clinical data as RMSEA < 0.05, CFI = 0.94, and χ 2/Df = 2.29. As the correlation between symptoms and related pattern factors evaluated to be with adequate factor loading, the instrument is of preliminary interpretation. Most precision of assessment could be achieved for patients with moderate severity of the pattern as shown in test information and standard error functions. CONCLUSIONS: An instrument with an interpretable conceptual framework was developed for pattern quantification in TCM clinical practice. By constructing and evaluating both psychological and physical effects in a multidimensional model of the TCM pattern of FD, the paradigm raised in this article provided a valuable reference for interpreting complex diseases and theories such as FD and TCM patterns.

Capsaicin-the major bioactive ingredient of chili peppers: bio-efficacy and delivery systems.

Capsaicin is the primary bioactive substance in red chili peppers, which produces the pungent flavor. During the past few decades, pharmacological benefits of capsaicin and its underlying mechanisms have been examined extensively. In this paper, major biological efficacies of capsaicin are reviewed, including analgesic, antioxidant, anti-inflammatory, anti-cancer, anti-obesity, cardio-protective, and metabolic modulation effects. Novel delivery systems, such as liposomes, micelles, micro/nano-emulsions, colloidal capsules and solid nanoparticles, for enhancing the oral bioavailability of capsaicin are also evaluated depending on the stability, encapsulation efficiency and biological properties. This review provides a theoretical basis for capsaicin to be further developed into a multi-functional ingredient with health-promoting functions in the nutraceutical industry.

Comparative study on the phytochemical profiles and cellular antioxidant activity of phenolics extracted from barley malts processed under different roasting temperatures.

Consumption of cereal foods has been related to health improvement, which is partly because of their phytochemicals. To explore the functionality and effective application of barley malt, a widely consumed nutritional food, the entire phytochemical profiles and bioactivities of three common barley malt products obtained under different roasting temperatures were analyzed. Results showed that they are abundant in phenolics including flavonoids with high antioxidative activities, as displayed by cellular antioxidant activity (CAA), oxygen radical absorbance capacity, peroxyl radical scavenging capacity, and DPPH and ABTS radical scavenging assays. Among the three barley malts, the raw barley malt bound extract and the dark barley malt free extract exhibited higher CAA values, while the raw barley malt contained a negligible amount of bound phenolics. An efficacious antiproliferation capacity of the dark barley malt free extract was detected in Caco-2 cells. Results also provide an insight into the positive attributes of thermal processing for the biofunctionality of barley malts, especially through the tuning of the accessibility and variability of beneficial phytochemicals.

Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation.

Dietary phenols are antioxidants with diverse physiological functions that are beneficial for human health. The objective of this research work was to investigate antioxidant activity of p-coumaric acid (p-CA) using four in vitro methods, the protective effects against oxidative stress in PC12 cells, and hypolipidemic effects on High fat-diet (HFD) mice model. The p-CA exhibited moderate antioxidant activity in the selected in vitro assay. The highest chelating activity of p-CA at 50 µg/mL was found to be 52.22%. Pretreatment with p-CA significantly enhanced cell viability of PC12 cell and suppressed AAPH-induced intracellular ROS generation and AAPH-induced LDH release. The hypolipidemic effects of p-CA (100 mg/kg BW) was directly linked to the increased expression of nuclear factor erythroid 2-related factor (Nrf2) by 2.0-fold, Glutathione peroxidase (Gpx) by 3.8-fold, Superoxide dismutase (SOD-1) by 1.6-fold, Heme oxygenase (HO-1) by 1.72-fold and NAD(P)H Quinone Dehydrogenase 1 (NQO-1) by 1.5-fold compared with HFD group. In addition to these effects, p-CA decreased total cholesterol and atherosclerosis index levels, and increased catalase (CAT) level in serum, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) levels in liver as compared HFD group. Administration of p-CA also promoted the recovery of hyperlipidemia steatohepatitis in mice by ameliorating lipid peroxidation. These results suggested that p-CA is a potent antioxidant with potential therapeutic efficacy for treating hyperlipidemia symptoms.

Importance of the Nucleophilic Property of Tea Polyphenols.

Tea is the second most popular beverage in the world after water. Vast accumulative evidence attest that tea consumption may promote human health, such as antioxidant, anti-obesity, and anticancer activities. Therefore, tea phytochemicals have drawn exceeding attention from researchers in structure confirmation, formation mechanism, component clarification, and bioactivity screening of interested constituents. Particularly, most investigations of chemical or biochemical reactions of catechins have concentrated on the B ring of the C6-C3-C6 skeleton. Hence, in this perspective, we reviewed the profound findings of the carbon-carbon (C-C) connection from the unambiguous characterization of novel A-ring addition derivatives of tea catechins, including catechin-carbonyl and catechin-theanine conjugates and the C-C formation mechanisms, and offered our view of the potential effects of catechin-carbonyl interactions on flavor generation and bioactive action in tea.

Feruloylated oligosaccharides from maize bran alleviate the symptoms of diabetes in streptozotocin-induced type 2 diabetic rats.

This study investigated the therapeutic effect of feruloylated oligosaccharides (FOs) extracted from maize bran on type 2 diabetic rats and its potential mechanism. Streptozotocin (STZ) induced type 2 diabetic male rats were orally administered with different levels of FOs for 8 weeks, and ferulic acid (FA) treatment was conducted as the positive control. Among all the treatments, the oral administration of 600 mg per kg bw per d FOs showed the best therapeutic effects on the diabetic rats by significantly lowering the levels of fasting plasma glucose (FPG), fasting insulin, TG, LDL-c, aspartate transaminase, creatine kinase and lactate dehydrogenase in plasma, while increasing the level of plasma HDL-c. In addition, the intake of FOs at 600 mg per kg bw per d exhibited the best antioxidant effects in the plasma, liver, kidney and heart of the diabetic rats, and the highest inhibitory effects on the formation of AGEs and CML in the organs, which might explain the alleviating effects of FOs on abdominal aorta injury observed in the current study. FOs presented better regulation effects on FPG, plasma lipid and the protection of abdominal aorta than FA under the same administered dosage. Based on these outcomes, FOs from maize bran could be beneficial for prevention or early treatment of diabetes mellitus.

Protective effect of rosmarinic acid and carnosic acid against streptozotocin-induced oxidation, glycation, inflammation and microbiota imbalance in diabetic rats.

This study evaluated the protective effects of two rosemary components, rosmarinic acid (RA) and carnosic acid (CA), against hypoglycemia, hyperlipidemia, oxidative stress and an imbalanced gut microbiota architecture in diabetic rats. Treatment with RA and CA (30 mg kg-1) decreased the levels of fasting plasma glucose (23.7%, 15.6%), total cholesterol (30.4%, 14.1%) and triglyceride (65.7%, 47.8%) at 15 weeks. RA and CA also exhibited an anti-oxidative and anti-glycative effect by lowering the formation of malondialdehyde and advanced glycation end products. In addition, they showed protective effects against tissue damage and inflammation in the abdominal aorta, based on microscopic observations and the analysis of protein expression. Finally, the prebiotic effects of RA and CA on gut microbiota were demonstrated by increasing the population of diabetes-resistant bacteria and decreasing the amounts of diabetes-sensitive bacteria. Overall, RA showed a stronger protective effect than CA in mitigating diabetic symptoms in rats.

Icariin ameliorates dexamethasone­induced bone deterioration in an experimental mouse model via activation of microRNA­186 inhibition of cathepsin K.

The present study aimed to investigate bone deterioration in glucocorticoid­induced osteoporosis (GIOP) mice, and the anti­osteoporosis effect and underlying molecular mechanism of icariin. Dexamethasone (DSM) treatment was demonstrated to facilitate the induction of hypercalciuria in GIOP mice. Icariin treatment reversed the dexamethasone (DXM)­induced disequilibrium of calcium homeostasis and bone resorption, and increased serum alkaline phosphatase, tartrate resistant acid phosphatase, osteocalcin and deoxypyridinoline. Haematoxylin and eosin staining revealed an increase in disconnections and separation in the trabecular bone network of the tibial proximal metaphysis, in the GIOP group. Icariin treatment reversed the DXM­induced trabecular deleterious effects, and stimulated bone remodeling in GIOP mice. Furthermore, the results demonstrated that the mRNA and protein expression of cathepsin K were significantly increased in GIOP mice, compared with the control group. Icariin treatment may suppress the expression of cathepsin K in the tibia of GIOP mice. The levels of microRNA (miR)­186 were markedly reduced in the tibia of GIOP mice compared with control group; however, this was inhibited by icariin treatment. Bioinformatics analysis demonstrated that miR­186 regulates cathepsin K via binding to the upstream 3'­untranslated region. Furthermore, transfection with miR­186 mimics resulted in inhibition of cathepsin K expression, whereas miR­186 inhibitors facilitated cathepsin K expression in osteoclasts. In conclusion, the present study demonstrated the protective effects of icariin against bone deteriorations in the experimental GIOP mice, and the underlying mechanism was mediated, at least partially, via activation of miR­186­mediated suppression of cathepsin K. These results provide evidence to support the use of icariin as a therapeutic approach in the management of glucocorticoid­induced bone loss, and the disequilibrium of calcium homeostasis.

p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities.

p-Coumaric acid (4-hydroxycinnamic acid) is a phenolic acid that has low toxicity in mice (LD50 = 2850 mg kg(-1) body weight), serves as a precursor of other phenolic compounds, and exists either in free or conjugated form in plants. Conjugates of p-coumaric acid have been extensively studied in recent years due to their bioactivities. In this review, the occurrence, bioavailability and bioaccessibility of p-coumaric acid and its conjugates with mono-, oligo- and polysaccharides, alkyl alcohols, organic acids, amine and lignin are discussed. Their biological activities, including antioxidant, anti-cancer, antimicrobial, antivirus, anti-inflammatory, antiplatelet aggregation, anxiolytic, antipyretic, analgesic, and anti-arthritis activities, and their mitigatory effects against diabetes, obesity, hyperlipaemia and gout are compared. Cumulative evidence from multiple studies indicates that conjugation of p-coumaric acid greatly strengthens its biological activities; however, the high biological activity but low absorption of its conjugates remains a puzzle. © 2015 Society of Chemical Industry.