Efficacy of Polyethylene Glycol Electrolyte Powder Combined with Linaclotide for Colon Cleansing in Patients with Chronic Constipation undergoing colonoscopy: a Multi-centre, single-blinded, Randomized-Controlled Trial.

BACKGROUND AND AIMS: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel-cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation. METHODS: This single-blinded, randomized, controlled and multicenter study was conducted from July 2021 to December 2022 at seven hospitals. Patients with chronic constipation who underwent colonoscopies were enrolled and randomly assigned to 4 groups with split -PEG regimens: 4L-PEG group, 4L-PEG+1d-Lin group, 3L-PEG+1d-Lin group, and 3L-PEG+3d-Lin group. The primary outcome was rates of adequate bowel preparation, defined as a total BBPS score ≥6 and a score ≥2 for each segment. Secondary outcomes were adverse effects, sleep quality, willingness to repeat the colonoscopy, adenoma detection rate, and polyp detection rate. RESULTS: 502 patients were enrolled. The rates of adequate bowel preparation (80.0% vs. 60.3%, P<0.001; 84.4% vs. 60.3%, P<0.001) and the total BBPS scores (6.90±1.28 vs. 6.00±1.61, P<0.001; 7.03±1.24 vs. 6.00±1.61, P<0.01) in 4L-PEG+1d-Lin group and 3L-PEG+3d-Lin group were superior to that in 4L-PEG group. Compared with 4L-PEG group, 4L-PEG+1d-Lin group (66.7% vs. 81.7%, P=0.008) and 3L-PEG+3d-Lin group (75.0% vs. 81.7%, P=0.224) had a lower percentage of mild adverse events. No statistically significant difference in willingness to repeat the colonoscopy, sleep quality, polyp detection rate, or adenoma detection rate was observed among groups. CONCLUSIONS: PEG combined with linaclotide might be an effective method for bowel preparation before colonoscopy in patients with chronic constipation.

Lithium Exposure and Risk of Major Neurocognitive Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). CONCLUSION: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

The component and structure of interpersonal trust.

Prior research has identified trust trait, trust expectation, trust risk and trust behavior as integral components of interpersonal trust. However, there still lack an in-depth exploration of the structural relationships among these integral components-how these integral components collectively constitute interpersonal trust. The current study innovatively proposed that interpersonal trust is anchored by individual trust trait, mediated by the dynamic equilibrium between trust risk and trust expectation, and culminates in trust behavior as the outcome. Interpersonal trust results from the synergistic interplay of individual and environmental factors. We called such structural relationships as the pyramid structure model of interpersonal trust, and proved its rationality by empirical evidence.

Establishment and application of a screening method for α-glucosidase inhibitors based on dual sensing and affinity chromatography.

α-Glucosidase plays a direct role in the metabolic pathways of starch and glycogen, any dysfunction in its activity could result in metabolic disease. Concurrently, this enzyme serves as a target for diverse drugs and inhibitors, contributing to the regulation of glucose metabolism in the human body. Here, an integrated analytical method was established to screen inhibitors of α-glucosidase. This step-by-step screening model was accomplished through the biosensing and affinity chromatography techniques. The newly proposed sensing program had a good linear relationship within the enzyme activity range of 0.25 U mL-1 to 1.25 U mL-1, which can quickly identify active ingredients in complex samples. Then the potential active ingredients can be captured, separated, and identified by an affinity chromatography model. The combination of the two parts was achieved by an immobilized enzyme technology and a microdevice for reaction, and the combination not only ensured efficiency and accuracy for inhibitor screening but also eliminated the occurrence of false positive results in the past. The emodin, with a notable inhibitory effect on α-glucosidase, was successfully screened from five traditional Chinese medicines using this method. The molecular docking results also demonstrated that emodin was well embedded into the active pocket of α-glucosidase. In summary, the strategy provided an efficient method for developing new enzyme inhibitors from natural products.

A comparative UHPLC-QTOF-MS/MS-based metabolomics approach reveals the metabolite profiling of wolfberry sourced from different geographical origins.

Wolfberry, known as Goji berry, is the fruit of Lycium barbarum L. (LB). As a famous functional food and TCM, the cost and efficacy of LB are closely linked to its geographical origin. The present study aimed to establish an effective method for distinguishing LB from different geographical origins. By employing UHPLC-QTOF-MS/MS combined with multivariate analysis, the metabolite profiling of LB (199 batches) obtained from Ningxia, Gansu, Qinghai, and Xinjiang, was evaluated. The results demonstrated that the method effectively distinguished LB from the four regions, with a total of 148 different metabolites being detected. Subsequent assessment using heat maps, Venn analysis, receiver operating characteristics curves and dot plots revealed 21 of these metabolites exhibited exceptional sensitivity and specificity, with under-curve values approaching 1, thus indicating their potential as biomarkers for LB. These findings strongly support the suitability of UHPLC-QTOF-MS/MS-based metabolomics as an effective approach to identify the source of LB.

Pharmacokinetic, Tissue Distribution, Metabolite, and Toxicity Evaluation of the Matrine Derivative, (6aS, 10S, 11aR, 11bR, 11cS)-10-Methylaminododecahydro-3a, 7a-Diaza-benzo (de) Anthracene-8-thione.

MASM, a structurally modified derivative of matrine, exhibits superior efficacy in reducing inflammation and liver injury in rats when compared to matrine. This study aims to investigate the pharmacokinetic profile and acute toxicity of MASM. Pharmacokinetic results revealed that MASM exhibited rapid absorption, with a Tmax ranging from 0.21 ± 0.04 h to 1.31 ± 0.53 h, and was eliminated slowly, with a t1/2 of approximately 10 h regardless of the route of administration (intravenous, intraperitoneal, or intragastric). The absolute intragastric bioavailability of MASM in rats was determined to be 44.50%, which was significantly higher than that of matrine (18.5%). MASM was detected in all rat tissues including the brain, and through the utilization of stable isotope-labeled compounds and standard references, ten metabolites of MASM, namely sophocarpine, oxysophocarpine, and oxymatrine, were tentatively identified. The LD50 of MASM in mice was determined to be 94.25 mg/kg, surpassing that of matrine (83.21 mg/kg) based on acute toxicity results. Histopathological and biochemical analysis indicated no significant alterations in the primary organs of the low- to medium-dosage groups of MASM. These findings provide valuable insights into the efficacy and toxicity profile of MASM.

The clinical application of transarterial embolization via radial artery in hemorrhagic diseases in obstetrics and gynecology.

Purpose: The present study aimed to explore the feasibility and safety of Transarterial embolization (TAE) in the treatment of obstetrics and gynecological hemorrhagic diseases transradial approach (TRA) compared to transfemoral approach (TFA). Methods: This cohort study was conducted on patients with obstetrics and gynecology bleeding diseases from June 2021 to November 2022. Clinical characteristics of the patients were comparable between the two groups. The success rate of puncture and embolization, radiation dose, operation time, fluoroscopy time (FT), as well as complications of each patient were recorded and then retrospectively analyzed the data. The European Five-dimensional Health Scale (ED-5Q) and visual analog scale (VAS) were used to assess the quality of life (QOL) on the day of discharge and 30 days after surgery between the two groups. Results: A total of 71 patients undergoing TAE were allocated to the TRA (n = 31) or TFA (n = 40) group in this study. Puncture and embolization were completed in all patients. Compared to the TFA group, the radiation dose of the TRA group (343.89 ± 108.81 mGy vs. 469.29 ± 198.66 mGy; p = 0.029) is significantly reduced. Minor complications occurred in only one patient (3.2%) in the TRA group. The surgery-related quality of life EQ-5D index score on the day of discharge in the TRA group (0.72 ± 0.12 vs. 0.65 ± 0.11; p = 0.017) was significantly higher than that in the TFA group, and the VAS score (2.55 ± 0.62 vs. 2.95 ± 0.85; p = 0.025) of catheter site discomfort was significantly lower in the TRA group were than in the TFA group, but no significant difference was observed in the QOL assessment at 30 days post-surgery. Conclusion: Transradial approach TAE has comparable efficacy and safety to TFA TAE in treating obstetrics and gynecological bleeding diseases. This access can improve patient QOL without affecting surgical safety.

Idiopathic pulmonary haemosiderosis misdiagnosed as haemolytic anaemia: a case report.

Idiopathic pulmonary haemosiderosis is a rare disease primarily affecting children. The condition is characterized by widespread bleeding from alveolar capillaries, resulting in symptoms such as haemoptysis, shortness of breath and iron deficiency anaemia. However, it is not a specific disease and sometimes can manifest solely as anaemia, which may be easily overlooked and misdiagnosed. The purpose of this case report was to describe a 1-year-old boy who exhibited haemolytic anaemia as the only symptom of idiopathic pulmonary haemosiderosis, with the intention of offering clinical insights into the precise diagnosis and subsequent management of this rare and easily misdiagnosed disease. Clinicians should keep idiopathic pulmonary haemosiderosis in mind when evaluating children with haemolytic anaemia and promptly initiate testing and treatment to prevent misdiagnosis and improve outcomes.

Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review.

Cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes involved in the biosynthesis and degradation of the endocannabinoids make up the endocannabinoid system (ECS). The components of the ECS are proven to modulate a vast bulk of various physiological and pathological processes due to their abundance throughout the human body. Such discoveries have attracted the researchers' attention and emerged as a potential therapeutical target for the treatment of various diseases. In the present article, we reviewed the discoveries of natural compounds, herbs, herbs formula, and their therapeutic properties in various diseases and disorders by modulating the ECS. We also summarize the molecular mechanisms through which these compounds elicit their properties by interacting with the ECS based on the existing findings. Our study provides the insight into the use of natural compounds that modulate ECS in various diseases and disorders, which in turn may facilitate future studies exploiting natural lead compounds as novel frameworks for designing more effective and safer therapeutics.

Valorization of sewage sludge for facile and green wood bio-adhesives production.

A method is presented herein for the design of wood bio-adhesives using sewage sludge extracts (SSE). SSE was extracted from SS using deep eutectic solvents and processed with glycerol triglycidyl ether (GTE) to disrupt the secondary structure of proteins. An additive was also used to improve mechanical performance. The resulting bio-adhesive (SSE/GTE@TA) had a wet shear strength of 0.93 MPa, meeting the Chinese national standard GB/T 9846-2015 (≥0.7 MPa). However, the high polysaccharide content in SSE would weaken the mechanical properties of wood bio-adhesives. The key to improve bio-adhesive quality was the formation of a strong chemical bond via Maillard reaction as well as higher temperatures (140 °C) to reduce polysaccharide content via dehydration. This approach has lower environmental impact and higher economic efficiency compared to incineration and anaerobic digestion of sewage sludge. This work provides a new perspective on the high-value utilization of SS and offers a novel approach to developing bio-adhesives for the wood industry.

The Effect of Organic Matter from Sewage Sludge as an Interfacial Layer on the Surface of Nano-Al and Fluoride.

Due to its high reactivity, the nano aluminum particle (n-Al) has attracted more attention in energetic materials but is easily oxidized during processing. In order to realize sewage sludge (SS) resource and n-Al coating, the organic matter was extracted from SS, using the deep eutectic solvent method due to its strong dissolving capacity, and then the organic matter was pretreated by ball milling, which was used as an interfacial layer between n-Al and fluoride. It was found that organic matter was successfully extracted from SS. The main organic matter is proteins. The ball milling method can effectively destroy the secondary structure of proteins to release more active functional groups. During the pretreatment, the Maillard reaction broke the proteins structure to form more active low molecular weight compounds. It was confirmed that n-Al can be coated by PBSP under mild conditions to form a uniform core-shell structure. PFOA can effectively coat the n-Al@PBSP to form n-Al@PBSP/PFOA, which can enhance the combustion of n-Al. The gas phase flame temperature can notably improve to 2892 K. The reaction mechanism between n-Al and coating was analyzed. The results could help SS treatment and provide new insights for n-Al coating and SS-based organic matter recovery and utilization.

Magnolol as STAT3 inhibitor for treating multiple sclerosis by restricting Th17 cells.

OBJECTIVE: Multiple sclerosis (MS) is an immune disease in the central nervous system (CNS) associated with Th17 cells. Moreover, STAT3 initiates Th17 cell differentiation and IL-17A expression through facilitating RORγt in MS. Here, we reported that magnolol, isolated from Magnolia officinalis Rehd. Et Wils, was regarded as a candidate for MS treatment verified by both in vitro and in vivo studies. METHODS: In vivo, experimental autoimmune encephalomyelitis (EAE) model in mice was employed to evaluate the alleviation of magnolol on myeloencephalitis. In vitro, FACS assay was employed to evaluate the effect of magnolol on Th17 and Treg cell differentiation and IL-17A expression; network pharmacology-based study was applied to probe the involved mechanisms; western blotting, immunocytochemistry, and luciferase reporter assay was used to further confirm the regulation of magnolol on JAK/STATs signaling pathway; surface plasmon resonance (SPR) assay and molecular docking were applied to manifest affinity with STAT3 and binding sites; overexpression of STAT3 was employed to verify whether magnolol attenuates IL-17A through STAT3 signaling pathway. RESULTS: In vivo, magnolol alleviated loss of body weight and severity of EAE mice; magnolol improved lesions in spinal cords and attenuated CD45 infiltration, and serum cytokines levels; correspondingly, magnolol focused on inhibiting Th17 differentiation and IL-17A expression in splenocyte of EAE mice; moreover, magnolol selectively inhibited p-STAT3(Y705) and p-STAT4(Y693) of both CD4+ and CD8+ T cells in splenocyte of EAE mice. In vitro, magnolol selectively inhibited Th17 differentiation and IL-17A expression without impact on Treg cells; network pharmacology-based study revealed that magnolol perhaps diminished Th17 cell differentiation through regulating STAT family members; western blotting further confirmed that magnolol inhibited p-JAK2(Y1007) and selectively antagonized p-STAT3(Y705) and slightly decreased p-STAT4(Y693); magnolol antagonized both STAT3 nucleus location and transcription activity; magnolol had a high affinity with STAT3 and the specific binding site perhaps to be at SH2 domain; overexpression of STAT3 resulted in failed inhibition of magnolol on IL-17A. CONCLUSION: Magnolol selectively inhibited Th17 differentiation and cytokine expression through selectively blocking of STAT3 resulting in decreased the ratio of Th17/Treg cells for treating MS, suggesting that the potential of magnolol for treating MS as novel STAT3 inhibitor.

Structural Characterization and Anti-Inflammatory Activity of a Novel Polysaccharide from Duhaldea nervosa.

In the present study, a novel water-soluble polysaccharide (DNP-1) was isolated and purified from the root of Duhaldea nervosa via column chromatography. Structural analyses indicated that DNP-1 had a linear backbone consisting of (2→1)-linked ß-D- fructofuranosyl residues, ending with a (2→1) bonded α-D-glucopyranose. DNP-1 was a homogeneous polysaccharide with an average molecular weight of 3.7 kDa. Furthermore, the anti-inflammatory activity of DNP-1 was investigated in vitro. The concentration of pro-inflammatory cytokines, including NO, TNF-α, MCP-1, IL-2, and IL-6, in the DNP-1 treatment group was suppressed in LPS-induced RAW 264.7 cells. DNP-1 was able to improve inflammatory injury by inhibiting the secretion of pro-inflammatory cytokines. These investigations into this polysaccharide from the root of Duhaldea nervosa provide a scientific basis for the further development of this plant. The results indicate that this Duhaldea nervosa polysaccharide could be used as a potential natural source for the treatment of inflammatory injury.

Technique to match mesorectal lymph nodes imaging findings to histopathology: node-by-node comparison.

BACKGROUND: Lymph node status is critical for staging rectal cancer and determining neoadjuvant therapy regimens. Establishing a matching between imaging and histopathological lymph nodes is fundamental for predicting lymph node status. This study reports a technique to achieve node-by-node pairing of mesorectal lymph nodes between imaging findings and histopathology. METHODS: Fifty-two patients with histopathologically verified rectal cancer underwent magnetic resonance imaging before surgery. The status of each lymph node in the surgical specimens was analyzed histopathologically and matched with preoperative imaging after the operation. RESULTS: A total of 346 mesorectal lymph nodes were located on imaging evaluation, of which 313 were confirmed histopathologically, and 33 were unmatched. The total success rate of the technique was 90.5%. Node-by-node analysis revealed 280 benign and 33 malignant nodal structures. CONCLUSION: The technique to match mesorectal lymph node imaging findings to histopathology was feasible and effective. It simplified the technical method and had a reasonable success matching rate, which could provide a standardized approach for obtaining a prospective correlation between imaging and histological findings, supporting all subsequent related studies at the level of mesorectal lymph nodes.

Serum and brain metabolomic study reveals the protective effects of Bai-Mi-Decoction on rats with ischemic stroke.

Bai-Mi-Decoction (BMD), which is composed of Eugenia caryophyllata, Myristica fragrans, Moschus berezovskii, and Crocus sativu, is a characteristic TCM multi-herb formula for brain disease. However, the mechanism of protective effects of BMD on ischemic stroke (IS) still has not been clarified. Our study is designed to elucidate the protective effects and underlying mechanisms of BMD on IS by employing pharmacodynamic and serum and brain metabolomic methods. In this experiment, 90 adult male Sprague-Dawley rats were randomly divided into the sham operation group (SHAM, vehicle), middle cerebral artery occlusion-reperfusion injury model group (MCAO/R, vehicle), positive control group (NMDP, 36 mg/kg/day nimodipine), and low (BMDL, 0.805 g/kg/day), moderate (BMDM, 1.61 g/kg/day), and high (BMDH, 3.22 g/kg/day) dosage of BMD prophylactic administration groups. The drugs were dissolved in 0.5% CMC-Na and orally administered to rats with equal volumes (100 g/ml body weight) once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, change in body weight, and serum NO, SOD, MDA, GSH, and GSSG levels were determined. Pathological abnormalities using hematoxylin and eosin staining and the expression of VEGF, caspase-3, and NF-κB were analyzed. Furthermore, serum and brain metabolic profiles were explored to reveal the underlying mechanism using UHPLC-QTOF-MS/MS technology. BMD exhibited significant neuroprotective effects on MCAO/R rats. As compared to the MCAO/R model group, it could reduce the neurological deficit score and cerebral infarct volume, increase body weight, enhance GSH, SOD, and GSSG activities, and decrease NO and MDA contents of MCAO/R rats. Meanwhile, BMD could ameliorate pathological abnormalities of MCAO/R rats through reducing neuronal loss, vacuolated spaces, shrunken neurons, and destructed neuron structure, as well as regulating the expression of VEGF, caspase-3, and NF-κB. UHPLC-QTOF-MS/MS-based serum and brain metabolomics analysis found a total of 53 differential metabolites between MCAO/R and SHAM groups, of which 30 were significantly regulated by BMD intervention, and further metabolic pathway analysis implied that the protective effects were mainly associated with amino acid and glycerophospholipid metabolisms. Our pharmacodynamic and metabolomic results revealed the neuroprotective effects of BMD on MCAO/R rats, and the underlying mechanisms were probably related to amino acid and glycerophospholipid metabolisms.

Perspectives of herbs and their natural compounds, and herb formulas on treating diverse diseases through regulating complicated JAK/STAT signaling.

JAK/STAT signaling pathways are closely associated with multiple biological processes involved in cell proliferation, apoptosis, inflammation, differentiation, immune response, and epigenetics. Abnormal activation of the STAT pathway can contribute to disease progressions under various conditions. Moreover, tofacitinib and baricitinib as the JAK/STAT inhibitors have been recently approved by the FDA for rheumatology disease treatment. Therefore, influences on the STAT signaling pathway have potential and perspective approaches for diverse diseases. Chinese herbs in traditional Chinese medicine (TCM), which are widespread throughout China, are the gold resources of China and have been extensively used for treating multiple diseases for thousands of years. However, Chinese herbs and herb formulas are characterized by complicated components, resulting in various targets and pathways in treating diseases, which limits their approval and applications. With the development of chemistry and pharmacology, active ingredients of TCM and herbs and underlying mechanisms have been further identified and confirmed by pharmacists and chemists, which improved, to some extent, awkward limitations, approval, and applications regarding TCM and herbs. In this review, we summarized various herbs, herb formulas, natural compounds, and phytochemicals isolated from herbs that have the potential for regulating multiple biological processes via modulation of the JAK/STAT signaling pathway based on the published work. Our study will provide support for revealing TCM, their active compounds that treat diseases, and the underlying mechanism, further improving the rapid spread of TCM to the world.

The Combination of Individual Herb of Mi-Jian-Chang-Pu Formula Exerts a Synergistic Effect in the Treatment of Ischemic Stroke in Rats.

Mi-Jian-Chang-Pu formula (MJCPF), composed of Crocus sativus L. and Acorus tatarinowii Schott, is a well-known TCM for treatment of hemiplegia, facial paralysis as well as language dysfunction caused by stroke both in ancient and modern times. By using pharmacodynamics, pharmacokinetics, and metabolomics, our present study discusses whether the combination of individual herbs or major active components of MJCPF possess synergistic neuroprotective effects against ischemic stroke (IS). 108 adult male Sprague-Dawley rats were randomly and equally divided into 9 groups, including sham group (N, vehicle), middle cerebral artery occlusion (MCAO) model group (M, vehicle), positive group (P, 36 mg/kg/day nimodipine), crocin I (A1, 40 mg/kg/day), ß-asarone (B1, 15 mg/kg/day), crocin I + ß-asarone (A1B1, 55 mg/kg/day), C. sativus (A, 580 mg/kg/day), A. tatarinowii (B, 480 mg/kg/day), and C. sativus + A. tatarinowii, also named MJCPF (AB, 1060 mg/kg/day) groups. All drugs were orally administered to rats once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, body weight change, TTC, HE and IHC staining, behavioral evaluation, metabolic profiles, and pharmacokinetic parameters were determined. MCAO led to severe brain damage including large infarct volume, more severe brain tissue injury, and worse neurological function as compared to the sham rats. All treatment groups showed a significant neuroprotective effect on MCAO rats. Furthermore, the pharmacodynamics' results demonstrated that MJCPF had a synergistic effect evidenced by small infarct volume, more regular arrangement of neuronal cells, and more improved neural function, and the levels of inflammatory factors were closer to normality. A total of 53 differential metabolites between MCAO and sham groups were screened by integration of serum and brain metabolisms, all of which were restored at varying degrees in treatment. PCA and PLS-DA analysis showed that the levels of differential metabolites treated with MJCPF were closer to the sham group than the individual herb and single compound alone or A1B1 combination. The pharmacokinetic parameters further verified the above results that MJCPF could synergistically promote drug absorption greater than others. Our integrated pharmacodynamics, metabolomics, and pharmacokinetic approach reveals the synergistic effect of MJCPF on treatment of IS, which powerfully contribute to the understanding of scientific connotation of TMC formula.

Integration of pharmacodynamics and metabolomics reveals the therapeutic effects of 6-acetylacteoside on ovariectomy-induced osteoporosis mice.

BACKGROUND: 6-acetylacteoside (6-AA) is a phenylethanoid glycoside isolated from Cistanche deserticola which had been previously proven to possess anti-osteoporotic activity previously. Currently, it is still unknown whether 6-AA plays a crucial role on the anti-osteoporotic effects of C. deserticola. PURPOSE: To elucidate the therapeutic effect and mechanism of 6-AA on osteoporosis by employing an ovariectomized mouse model in vivo and RAW264.7 cells in vitro. METHODS: Sixty female ICR mice were randomly assigned into six groups: sham-operated control group (SHAM, vehicle), ovariectomized model group (OVX, vehicle), positive group (EV, 1 mg/kg/day of estradiol valerate), low dosage (10 mg/kg/day of 6-AA), medium dosage (20 mg/kg/day of 6-AA) and high dosage (40 mg/kg/day of 6-AA) treatment groups. All substances were administered daily by intragastric gavage. After 12 weeks of intervention, trabecular bone microarchitecture was estimated and bone biomechanics were determined. Bone formation and resorption factors were determined by using the corresponding Elisa kits. The related proteins and metabolites were estimated by using western-blot and metabolomics techniques. RESULTS: OVX mice demonstrated significant atrophy of the uterine and vagina, declined biomechanical parameters such as flexural strength and maximum load, deteriorated trabecular bone microarchitecture such as decreased BMD, BMC, TMC, TMD, BVF, Tb. N, and Tb. Th and increased Tb. Sp, as well as increased bone resorption factors such as TRAP, cathepsin K, and DPD, all after 12 weeks of ovariectomy operation. Following administration of 6-AA to OVX mice, parameters related to the bone microarchitecture, bone resorption activities as well as biomechanical properties were all significantly improved. Meanwhile, the levels of NF-κB, NFATc1, RANK, RANKL and TRAF6 were significantly downregulated, while OPG, PI3K and AKT were upregulated after 6-AA intervention. This indicates that, 6-AA could prevent bone resorption by regulating the RANKL/RANK/OPG mediated NF-κB and PI3K/AKT pathways. Furthermore, 26 different metabolites corresponding to 25 metabolic pathways were identified, and 5 of which were related to the formation of osteoporosis. Interestingly, 23 abnormal metabolites were recovered after 6-AA treatment. CONCLUSION: Our results revealed the significant anti-osteoporotic effects of 6-AA on ovariectomized mice which were probably exerted via suppression of osteoclast formation and bone resorption.