Uric acid-lowering effect of harpagoside and its protective effect against hyperuricemia-induced renal injury in mice.

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

Anterior cervical corpectomy and fusion-derived adjacent segment disease managed via channel-repairing anterior endoscopic transcorporeal cervical discectomy: a case report.

BACKGROUND: Management of anterior cervical corpectomy and fusion (ACCF)-derived adjacent segment disease (ASD) represented a challenge facing the surgeons. METHODS: A 41-year man diagnosed as C3-4 level ASD derived from C5-level ACCF surgery 13 years ago was admitted to the hospital for numbness and pain in the right shoulder and upper limb. Percutaneous full-endoscopic anterior transcorporeal cervical discectomy (PEATCD) was performed, and pre- and postoperative clinical and imaging data were collected. RESULTS: The operation was completed within 70 min, and no clinical or radiological complication was reported. The visual analog scale (VAS) score decreased from preoperative 5 points to postoperative 1 point. Numbness was relieved postoperatively and disappeared completely at postoperative 3 months. Imaging data indicated sufficient spinal cord decompression, good channel repairing and cervical alignment. CONCLUSIONS: Channel-repairing PEATCD was successfully performed to treat ACCF-derived ASD, nevertheless, the long-term efficacy remained tracing and further clinical trials were needed to validate its efficacy.

Phomopsterone B Alleviates Liver Fibrosis through mTOR-Mediated Autophagy and Apoptosis Pathway.

Liver fibrosis is the initial pathological process of many chronic liver diseases. Targeting hepatic stellate cell (HSC) activation is an available strategy for the therapy of liver fibrosis. We aimed to explore the anti-liver fibrosis activity and potential mechanism of phomopsterone B (PB) in human HSCs. The results showed that PB effectively attenuated the proliferation of TGF-ß1-stimulated LX-2 cells in a concentration-dependent manner at doses of 1, 2, and 4 µM. Quantitative real-time PCR and Western blot assays displayed that PB significantly reduced the expression levels of α-SMA and collagen I/III. AO/EB and Hoechst33342 staining and flow cytometry assays exhibited that PB promoted the cells' apoptosis. Meanwhile, PB diminished the number of autophagic vesicles and vacuolated structures, and the LC3B fluorescent spots indicated that PB could effectively inhibit the accretion of autophagosomes in LX-2 cells. Moreover, rapamycin and MHY1485 were utilized to further investigate the effect of mTOR in autophagy and apoptosis. The results demonstrated that PB regulated autophagy and apoptosis via the mTOR-dependent pathway in LX-2 cells. In summary, this is the first evidence that PB effectively alleviates liver fibrosis in TGF-ß1-stimulated LX-2 cells, and PB may be a promising candidate for the prevention of liver fibrosis.

Three New Selaginellin Derivatives from Selaginella pulvinata and Their α-Glucosidase Inhibitory Activity.

Three new selaginellin derivatives, selaginpulvilins V-X (1-3), together with seven known analogs (4-10) were isolated from whole plants of Selaginella pulvinata. Their structures were determined by extensive spectroscopic methods including 1D and 2D NMR, HR-ESI-MS and chemical derivatization method. Compound 1 represents a rare example of naturally occurring selaginellin with an alkynylphenol-trimmed skeleton. Biological evaluation showed that compounds 2, 6 and 8 displayed moderate inhibition against α-glucosidase with IC50 values of 3.71, 2.04 and 4.00 µM, respectively.

An Internal Defect Detection Algorithm for Concrete Blocks Based on Local Mean Decomposition-Singular Value Decomposition and Weighted Spatial-Spectral Entropy.

Within the scope of concrete internal defect detection via laser Doppler vibrometry (LDV), the acquired signals frequently suffer from low signal-to-noise ratios (SNR) due to the heterogeneity of the concrete's material properties and its rough surface structure. Consequently, these factors make the defect signal characteristics challenging to discern precisely. In response to this challenge, we propose an internal defect detection algorithm that incorporates local mean decomposition-singular value decomposition (LMD-SVD) and weighted spatial-spectral entropy (WSSE). Initially, the LDV vibration signal undergoes denoising via LMD and the SVD algorithms to reduce noise interference. Subsequently, the distribution of each frequency in the scan plane is analyzed utilizing the WSSE algorithm. Since the vibrational energy of the frequencies caused by the defect resonance is concentrated in the defect region, its energy distribution in the scan plane is non-uniform, resulting in a significant difference between the defect resonance frequencies' SSE values and the other frequencies' SSE values. This feature is used to estimate the resonant frequencies of internal defects. Ultimately, the defects are characterized based on the modal vibration patterns of the defect resonant frequencies. Tests were performed on two concrete blocks with simulated cavity defects, using an ultrasonic transducer as the excitation device to generate ultrasonic vibrations directly from the back of the blocks and applying an LDV as the acquisition device to collect vibration signals from their front sides. The results demonstrate the algorithm's capacity to effectively pinpoint the information on the location and shape of shallow defects within the concrete, underscoring its practical significance for concrete internal defect detection in practical engineering scenarios.

Concrete Multi-Type Defect Classification Algorithm Based on MSSMA-SVM.

In order to realize the automatic classification of internal defects for non-contact nondestructive testing of concrete, a concrete multi-type defect classification algorithm based on the mixed strategy slime mold algorithm support vector machine (MSSMA-SVM) was proposed. The concrete surface's vibration signal was obtained using a laser Doppler vibrometer (LDV) for four classification targets for no defect, segregation, cavity, and foreign matter concrete classification targets. The wavelet packet transform (WPT) decomposes the detected signals to get information on different frequency bands. The energy ratio change rate, energy ratio, and wavelet packet singular entropy of each node after the WPT were used as the feature input of MSSMA-SVM. The experimental results show that the designed MSSMA-SVM classifier can accurately detect the type, which provides a practical algorithm for classifying concrete defects by laser vibration measurement.

New Meroterpenoid and Isocoumarins from the Fungus Talaromyces amestolkiae MST1-15 Collected from Coal Area.

Three new compounds including a meroterpenoid (1) and two isocoumarins (8 and 9), together with thirteen known compounds (2-7, 10-16) were isolated from the metabolites of Talaromyces amestolkiae MST1-15. Their structures were identified by a combination of spectroscopic analysis. The absolute configuration of compound 1 was elucidated on the basis of experimental and electronic circular dichroism calculation, and compounds 8 and 9 were determined by Mo2(OAc)4-induced circular dichroism experiments. Compounds 7-16 showed weak antibacterial activities against Stenotrophomonas maltophilia with MIC values ranging from 128 to 512 µg/mL (MICs of ceftriaxone sodium and levofloxacin were 128 and 0.25 µg/mL, respectively).

Water-Air Interface Imaging: Recovering the Images Distorted by Surface Waves via an Efficient Registration Algorithm.

Imaging through the wavy water-air interface is challenging since the random fluctuations of water will cause complex geometric distortion and motion blur in the images, seriously affecting the effective identification of the monitored object. Considering the problems of image recovery accuracy and computational efficiency, an efficient reconstruction scheme that combines lucky-patch search and image registration technologies was proposed in this paper. Firstly, a high-quality reference frame is rebuilt using a lucky-patch search strategy. Then an iterative registration algorithm is employed to remove severe geometric distortions by registering warped frames to the reference frame. During the registration process, we integrate JADE and LBFGS algorithms as an optimization strategy to expedite the control parameter optimization process. Finally, the registered frames are refined using PCA and the lucky-patch search algorithm to remove residual distortions and random noise. Experimental results demonstrate that the proposed method significantly outperforms the state-of-the-art methods in terms of sharpness and contrast.

miR-23a-3p regulated by LncRNA SNHG5 suppresses the chondrogenic differentiation of human adipose-derived stem cells via targeting SOX6/SOX5.

Cartilage generation and degradation are controlled by miRNAs. Our previous study showed miR-23a-3p was downregulated during chondrogenic differentiation in chondrogenic human adipose-derived mesenchymal stem cells (hADSCs). In the present study, we explored the function of miR-23a-3p in chondrogenesis differentiation. The role of miR-23a-3p in chondrogenic differentiation potential of hADSCs was assessed by Alcian blue staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. We show that miR-23a-3p suppressed the chondrogenic differentiation of hADSCs. LncRNA SNHG5 interacted with miR-23a-3p, and suppression or overexpression of SNHG5 correlates with inhibition and promotion of hADSC chondrogenic differentiation, respectively. We have determined that SNHG5 can sponge miR-23a-3p to regulate the expression of SOX6/SOX5, transcription factors that play essential roles in chondrocyte differentiation. Furthermore, the overexpression of SNHG5 activates the JNK/MAPK/ERK pathway. In conclusion, miR-23a-3p regulated by lncRNA SNHG5 suppresses the chondrogenic differentiation of human adipose-derived stem cells via targeting SOX6/SOX5.

Kinetic Resolution of Allylic Alcohol with Chiral BINOL-Based Alkoxides: A Combination of Experimental and Theoretical Studies.

The development and characterization of enantioselective catalytic kinetic resolution of allylic alcohols through asymmetric isomerization with chiral BINOL derivatives-based alkoxides as bifunctional Brønsted base catalysts were described in the study. A number of chiral BINOL derivatives-based alkoxides were synthesized, and their structure-enantioselectivity correlation study in asymmetric isomerization identified a promising chiral Brønsted base catalyst, which afforded various chiral secondary allylic alcohols (ee up to 99%, S factor up to >200). In the mechanistic study, alkoxide species were identified as active species and the phenol group of BINOL largely affected the high reactivity and enantioselectivity via hydrogen bonding between the chiral Brønsted base catalyst and substrates. The strategy is the first successful synthesis strategy of various chiral secondary allylic alcohols through enantioselective transition-metal-free base-catalyzed isomerization. The applicability of the strategy had been demonstrated by the synthesis of the bioactive natural product (+)-veraguensin.

Percutaneous full-endoscopic anterior transcorporeal cervical discectomy and channel repair: a technique note report.

BACKGROUND: Compared to anterior cervical discectomy and fusion (ACDF), cervical motion segment and disc was retained through anterior transcorporeal herniotomy (ATH). But surgical field and manipulation in traditional ATH was restricted by the narrow channel. Percutaneous full-endoscopic transdiscal cervical discectomy is a minimally invasive and functional spine surgery. However, significant loss of intervertebral disc height was inevitable. This study was done to illustrate the feasibility, safety, and efficacy and present our surgical experience of percutaneous full-endoscopic anterior transcorporeal cervical discectomy (PEATCD) and channel repair (CR) for the treatment of cervical disc herniation (CDH). METHODS: Four patients with CDH were chosen to undergo PEATCD and CR with a follow-up care for at least 22 months. The visual analogue score (VAS), Japanese Orthopedic Association (JOA), and modified Macnab criteria were recorded during the postoperative periods. CT images were obtained to observe the healing of the channel at 1 week and 3 months after the operation. RESULTS: The average operating time was 83.75 min. Drainage tubes were unnecessary. No procedure-related complications occurred. The postoperative VAS and JOA scores were improved compared to those of the preoperative assessment. The clinical efficacy was excellent in 3 patients and good in 1 patient at final follow up stage according to the modified Macnab criteria. The hernia was removed completely in all patients according to postoperative MRI. Migration of the repair implementation and collapse of the drilled vertebrae were not observed during the postoperative periods. The bony channel was nearly absent on CT images obtained at 3 months postoperative. CONCLUSION: This is the first time that the anterior transcorporeal cervical discectomy and CR have been performed simultaneously under endoscopy. Less damage to disc and the retained cervical motion segment were achieved through this method. This is a feasible, safe, and minimally invasive procedure. TRIAL REGISTRATION: Numbers: ChiCTR1800016383 . Registered 29 may 2018. Retrospectively registered. TRIAL REGISTRY: Chinese Clinical Trial Registry.

Organocatalytic Intramolecular [4+2] Cycloaddition between In Situ Generated Vinylidene ortho-Quinone Methides and Benzofurans.

Described herein is the enantioselective construction of oxygen-containing [5-6-5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho-quinone methides and benzofurans. According to this methodology, a series of oxygen-containing [5-6-5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio- and diastereoselectivities (>99 % ee, >20:1 d.r.). Furthermore, the deuterium-labeling experiments and high-resolution mass spectroscopy demonstrated that a vinylidene ortho-quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2-ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram-scale synthesis were achieved for this transformation.

Organocatalytic Asymmetric Synthesis of Chiral Dioxazinanes and Dioxazepanes with in Situ Generated Nitrones via a Tandem Reaction Pathway Using a Cooperative Cation Binding Catalyst.

Heterocyclic skeletons play major roles in pharmaceuticals and biological processes. Cycloaddition reactions are most suitable synthetic tools to efficiently construct chemically diverse sets of heterocycles with great structural complexity owing to the simultaneous or sequential formation of two or more bonds, often with a high degree of selectivity. Herein, we report an unprecedented formal cycloaddition of N-Boc-N-hydroxy amido sulfones as the nitrone precursors with terminal-hydroxy α,ß-unsaturated carbonyls in the presence of Song's chiral oligoethylene glycol as a cation-binding catalyst and KF as a base to afford a wide range of highly enantio- and diastereo-enriched six-membered dioxazinane and seven-membered dioxazepane heterocycles. In this process, nitrones as well as terminal-hydroxy α,ß-unsaturated carbonyls serve as "amphiphilic" building units, and the reaction proceeds through a tandem pathway sequence of oxa-Mannich reaction/oxa-Michael reaction/tautomerization/protonation. The cation-binding catalysis in a densely confined chiral space in situ formed by the incorporation of potassium salt is the key to this successful catalysis. This strategy opens a new pathway for the asymmetric synthesis of diverse heterocyclic skeletons of great complexity.

Environmental investigations and molecular typing of Aspergillus in a Chinese hospital.

Invasive fungal infections due to Aspergillus species have become a major cause of morbidity and mortality among immunocompromised patients. In order to determine the possible relationship between environmental contamination by Aspergillus and the occurrence of invasive aspergillosis, a 1-year prospective study was carried out in a tertiary hospital in China. Air, surface, and tap water sampling was performed twice monthly at the bone marrow transplant (BMT) department, intensive care unit (ICU), neurosurgery intensive care unit (NICU), and outdoors. Nose, pharynx, and sputum samples were collected from high-risk patients. Isolates of Aspergillus from the environment and patients were genotyped by random amplification of polymorphic DNA (RAPD) assay to investigate the origin of infection. Mean total Aspergillus count was 7.73, 8.94, 13.19, and 17.32 cfu/m(3) in the BMT department, ICU, NICU, and outdoors, respectively. RAPD analysis by R108 primer demonstrated that strains isolated from patients in NICU were identical to the environmental strain. Strains isolated from patients in ICU differed from the environmental strain. Aspergillus contamination was found in the BTM department, NICU, and ICU. Clinical and environmental strains from NICU had identical genotypes. These findings suggest that Aspergillus is found in the hospital environment including the air, surface, and tap water. The genotypes of Aspergillus were identical from patients and the environment, suggesting that clinical infection may originate from the hospital environment.

Management for degenerative lumbar spondylolisthesis: a network meta-analysis and systematic review basing on randomized controlled trials.

BACKGROUND: Consensus on the various interventions for degenerative lumbar spondylolisthesis (DLS) remains unclear. MATERIALS AND METHODS: The authors searched PubMed, Embase, Cochrane Library, Web of Science, and major scientific websites until 01 November 2023, to screen eligible randomized controlled trials (RCTs) involving the treatment of DLS. The seven most common DLS interventions [nonsurgical (NS), decompression only (DO), decompression plus fusion without internal fixation (DF), decompression plus fusion with internal fixation (DFI), endoscopic decompression plus fusion (EDF), endoscopic decompression (ED), and circumferential fusion (360F)] were compared. The primary (pain and disability) and secondary (complications, reoperation rate, operation time, blood loss, length of hospital stay, and satisfaction) outcomes were analyzed. RESULTS: Data involving 3273 patients in 16 RCTs comparing the efficacy of different interventions for DLS were reported. In terms of improving patient pain and dysfunction, there was a significant difference between surgical and NS. EDF showed the greatest improvement in short-term and long-term dysfunction (probability, 7.1 and 21.0%). Moreover, EDF had a higher complication rate (probability 70.8%), lower reoperation rate (probability, 20.2%), and caused greater blood loss (probability, 82.5%) than other surgical interventions. Endoscopic surgery had the shortest hospitalization time (EDF: probability, 42.6%; ED: probability, 3.9%). DF and DFI had the highest satisfaction scores. CONCLUSIONS: Despite the high complication rate of EDF, its advantages include improvement in pain, lower reoperation rate, and shorter hospitalization duration. Therefore, EDF may be a good option for patients with DLS as a less invasive surgical approach.

The role of TNF-α in osteoporosis, bone repair and inflammatory bone diseases: A review.

Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine synthesised primarily by mononuclear cells; it has a potent pro-inflammatory effect, playing a crucial role in metabolic, immune, and inflammatory diseases. This cytokine has been studied in various biological systems. In bone tissue, TNF-α plays an integral role in skeletal disorders such as osteoporosis, fracture repair and rheumatoid arthritis through its involvement in regulating the balance between osteoblasts and osteoclasts, mediating inflammatory responses, promoting angiogenesis and exacerbating synovial proliferation. The biological effect TNF-α exerts in this context is determined by a combination of the signalling pathway it activates, the type of receptor it binds, and the concentration and duration of exposure. This review summarises the participation and pathophysiological role of TNF-α in osteoporosis, bone damage repair, chronic immunoinflammatory bone disease and spinal cord injury, and discusses its main mechanisms.

Percutaneous Fully-endoscopic Anterior Transcorporeal Procedure for the Treatment of Isolated Ossification of the Posterior Longitudinal Ligament in the Cervical Spine: A Case Report.

BACKGROUND: With the development of spinal endoscopic techniques, on the basis of our previous experience in treating various types of cervical disc herniation with this endoscopic technique, we took the lead in applying the percutaneous fully endoscopic anterior transcorporeal procedure to be utilized in the treatment of the isolated cervical ossification of the posterior longitudinal ligament (OPLL). CASE PRESENTATION: A 66-year-old male patient who weighed 57 kg, with a height of 169 cm was admitted to the hospital on September 16, 2021 because of recurrent pain and numbness in the neck, shoulder, and right arm for 2 years, which as aggravated for the last 2 weeks. Two years ago, the patient developed neck and shoulder pain accompanied by right arm pain without obvious predisposing factors, and numbness in the first web space of the right hand. In the last 2 weeks, he had difficulty moving the right arm, but no pain or numbness in the contralateral arm. MRI and CT scans demonstrated that the ossified posterior longitudinal ligament of the cervical 5/6 vertebrae with spinal canal stenosis and seriously compressed the spinal cord patient was treated with a percutaneous fully endoscopic anterior transcorporeal procedure. CONCLUSION: Our percutaneous fully endoscopic anterior transcorporeal procedure is a feasible, minimally invasive surgery for treating isolated ossification of the posterior longitudinal ligament in the cervical spine.

Surgical Essentials and 2-Year Follow-Up Results of Channel Repair in Endoscopic Transcorporeal Discectomy for Cervical Disc Herniation.

OBJECTIVE: To evaluate long-term outcomes and surgical essentials of channel repair in endoscopic transcorporeal discectomy for cervical disc herniation. METHODS: From October 2019 to March 2020, 24 patients with cervical disc herniation underwent channel repair after percutaneous full-endoscopic anterior transcorporeal cervical discectomy. Five interventions were performed at C3-C4, 11 were performed at C4-C5, and 8 were performed at C5-C6. Clinical outcomes were evaluated by Neck Disability Index, Japanese Orthopaedic Association, and visual analog scale scores. Radiologic changes were evaluated with intervertebral disc height and drilled vertebral height. RESULTS: All procedures were completed with a mean operating time of 86.40 ± 8.19 minutes. Swollen neck was observed in 5 patients, which resolved within 2 hours. At the final follow-up, Neck Disability Index, Japanese Orthopaedic Association, and visual analog scale scores were improved significantly compared with preoperative assessments (P < 0.05); intervertebral disc height was decreased significantly (P < 0.05); and loss of drilled vertebral height was not significant (P > 0.05). All 24 bony channels disappeared by 3 months postoperatively. No other complications were observed. CONCLUSIONS: Percutaneous full-endoscopic anterior transcorporeal cervical discectomy with channel repair offers a minimally invasive and effective treatment option for patients with cervical disc herniation. This technique demonstrates favorable clinical outcomes, including preservation of cervical spine mobility and minimal complications. Although there was a significant loss of intervertebral disc height, no vertebral collapse occurred. Strict adherence to surgical indications and precautions is crucial for successful outcomes. Further research and long-term studies are required to validate the efficacy and safety of this approach in a larger patient population.

[Association analysis between mixed exposure to phenols and semen quality].

Phenols such as bisphenols, parabens, and triclosan are common environmental endocrine disruptors. Previous epidemiological studies have suggested that phenols may affect semen quality, but the results were inconsistent. In addition, most existing studies have been limited to the effects of a single chemical compound, ignoring the health effects of mixed exposure to multiple chemicals. Thus, we aimed to explore the associations between individual and mixed exposure to phenols and various semen quality parameters. In this study, a rapid and sensitive method was used to determine 18 phenolic compounds in urine samples of 799 volunteers who donated sperm samples to the Shanghai Human Sperm Bank. A spot urine sample was collected from each subject on the day of their clinic visit and stored at -20 ℃ until testing. Urine samples (200 µL) were extracted and added with 20 µL of an internal standard and 50 µL of ß-glucuronidase solution. The mixtures were then incubated for 12 h at 37 ℃. After hydrolysis, the samples were extracted twice using ethyl acetate (500 µL). The concentrations of the 18 phenolic compounds were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Semen quality parameters were analyzed using a computer-aided semen analyzer. Multiple linear regressions were used to detect the associations between individual phenol exposure and semen quality parameters. In addition, weighted quantile sum (WQS) models were used to explore the associations between mixed-phenol exposure and semen quality parameters. After adjusting for potential covariates, the results of multiple linear regressions showed that exposure to ethyl paraben (EtP) was significantly negatively associated with sperm concentration and total sperm count (P<0.05). In addition, exposure to mixed phenols was significantly associated with decreased sperm concentration; methyl paraben (MeP) and EtP were identified as the main contributors to this decrease. Thus, phenol exposure may be associated with decreased semen quality in young males, particularly with respect to sperm concentration and total sperm count.

Withanolides from the active extract of Physalis angulate and their anti-hepatic fibrosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.