Huangtu decoction alleviates chronic diarrhea of spleen-yang deficiency in mice by altering host metabolome and intestinal microbiota composition.

BACKGROUND: Huangtu decoction (HTD), a traditional Chinese medicine recipe, warms the spleen, nourishes the blood, and stops bleeding. It has been used to treat dysentery, gastrointestinal bleeding, diarrhea, and other symptoms caused by spleen-yang deficiency for more than 2,000 years in China. However, the mechanism underlying the treatment of chronic diarrhea due to spleen-yang deficiency (CDSD) using HTD remains unclear. AIMS: This study investigated whether HTD could mediate intestinal flora and serum metabolites to improve CDSD symptoms using a mouse model. METHODS: A CDSD mouse model induced by senna and an abnormal diet was constructed. The regulatory effects of HTD at 12.5, 25.0, and 50.0 g/kg/d on CDSD mice were assessed by measuring their bodyweight, diarrhea rate, loose stool rate, and histopathology. Changes in the intestinal flora of CDSD mice were analyzed by 16S rRNA gene sequencing. Untargeted serum metabolomic analysis was performed using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS). RESULTS: HTD had a modulating effect on CDSD by reducing the weight loss, diarrhea rate, loose stool rate, and pathologic damage. Intestinal flora analysis showed that HTD altered the community composition by decreasing the abundance of Allobaculum, Lactobacillus, and Ruminococcus. Serum metabolomics revealed that ascorbate and aldarate metabolism, aldosterone synthesis and secretion, platelet activation, hypoxia-inducible factor 1 signaling pathway, inositol phosphate metabolism, phosphatidylinositol signaling, galactose metabolism, and alpha-linolenic acid metabolism were modulated after HTD treatment. CONCLUSION: HTD may alleviate CDSD symptoms by reducing weight loss, diarrhea rate, loose stool rate, and pathologic damage caused by modeling and regulating intestinal flora and serum metabolites in CDSD mice.

Rapid identification of medicinal plants via visual feature-based deep learning.

BACKGROUND: Traditional Chinese Medicinal Plants (CMPs) hold a significant and core status for the healthcare system and cultural heritage in China. It has been practiced and refined with a history of exceeding thousands of years for health-protective affection and clinical treatment in China. It plays an indispensable role in the traditional health landscape and modern medical care. It is important to accurately identify CMPs for avoiding the affected clinical safety and medication efficacy by the different processed conditions and cultivation environment confusion. RESULTS: In this study, we utilize a self-developed device to obtain high-resolution data. Furthermore, we constructed a visual multi-varieties CMPs image dataset. Firstly, a random local data enhancement preprocessing method is proposed to enrich the feature representation for imbalanced data by random cropping and random shadowing. Then, a novel hybrid supervised pre-training network is proposed to expand the integration of global features within Masked Autoencoders (MAE) by incorporating a parallel classification branch. It can effectively enhance the feature capture capabilities by integrating global features and local details. Besides, the newly designed losses are proposed to strengthen the training efficiency and improve the learning capacity, based on reconstruction loss and classification loss. CONCLUSIONS: Extensive experiments are performed on our dataset as well as the public dataset. Experimental results demonstrate that our method achieves the best performance among the state-of-the-art methods, highlighting the advantages of efficient implementation of plant technology and having good prospects for real-world applications.

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. AIM OF THE STUDY: We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. MATERIALS AND METHODS: An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. RESULTS: We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. CONCLUSIONS: These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

Bear Bile Powder Improves Ulcerative Colitis by Protecting the Intestinal Mechanical Barrier and Regulating Intestinal Flora.

BACKGROUND: Bear Bile Powder (BBP) is a traditional Chinese medicine. It has been widely used in clinical practices and has shown a good anti-inflammatory effect. However, its effectiveness in treating Ulcerative Colitis (UC) has not yet been studied. OBJECTIVE: To explore the therapeutic effect of BBP on ulcerative colitis and its potential mechanism by combining acute ulcerative colitis mouse models and comprehensively observing various physiological and biochemical indexes of mice. METHODS: The acute ulcerative colitis model was induced by drinking water containing dextran sulfate sodium salt (DSS) for 7 days. Studies were divided into Control, DSS, DSS+ Sulfasalazine (SASP, 450 mg/kg), and DSS + bear bile powder group (BBP, 320 mg/kg). The Disease Activity Index (DAI) and colonic tissue damage of mice were evaluated. Tissue immunofluorescence and western blot were used to determine related tight Junction Proteins (TJs), and 16S V34 amplicon was used to analyze intestinal microorganisms. The therapeutic effect of BBP on ulcerative colitis model mice was studied comprehensively. RESULTS: After treatment, BBP can significantly improve the physiological condition of acute UC mice and reduce DAI fraction. Compared with the DSS group, the BBP group significantly increased the colon length and significantly decreased the injury fraction of acute UC mice. Regarding the intestinal mechanical barrier, BBP significantly increased the expression of ZO-1, Occludin, and Claudin 1 protein in colon tissue. In terms of microbial community, the intestinal microbial diversity of mice decreased after the administration of BBP, but there was no significant difference in structural composition between the BBP group and the Control group. By comparing the four groups of species with significant differences, it was found that the BBP group significantly reduced the abundance of specific harmful microorganisms at the order, family, genus, and species levels. CONCLUSION: Oral administration of a certain dose of BBP can significantly improve the symptoms of ulcerative colitis in mice. Part of the reason may be that it increases the expression of tight junction proteins, regulates specific flora in the intestine of mice, and maintains intestinal barrier homeostasis. In the future, the clinical application value of BBP will be explored, and BBP will be developed as a drug with the potential to treat UC and alleviate the pain of UC patients.

Aggregated parameter update schemes for monitoring binary profiles.

Profile monitoring is one of the most important topics for statistical process control. Traditional self-starting profile monitoring schemes generally use all historical observations to estimate parameters. Because of the rapid increase in the complexity of modern statistical processes, the practitioners often need to deal with massive datasets in process monitoring. However, when observations of each period are of large sample size and the computation is of high complexity, the traditional method is not economical and urgently needs a parameter update strategy. Under the framework of binary profile monitoring, this paper proposes a novel recursive update strategy based on the aggregated estimation equation (AEE) for massive datasets and designs a self-starting control chart accordingly. Numerical simulation verifies that the proposed method performs better in parameter estimation and process monitoring. In addition, we give the asymptotic property of the proposed monitoring statistic and illustrate our method's superiority by a real-data example.

circEPB41L2 blocks the progression and metastasis in non-small cell lung cancer by promoting TRIP12-triggered PTBP1 ubiquitylation.

The metastasis of non-small cell lung cancer (NSCLC) is the leading death cause of NSCLC patients, which requires new biomarkers for precise diagnosis and treatment. Circular RNAs (circRNAs), the novel noncoding RNA, participate in the progression of various cancers as microRNA or protein sponges. We revealed the mechanism by which circEPB41L2 (hsa_circ_0077837) blocks the aerobic glycolysis, progression and metastasis of NSCLC through modulating protein metabolism of PTBP1 by the E3 ubiquitin ligase TRIP12. With ribosomal RNA-depleted RNA seq, 57 upregulated and 327 downregulated circRNAs were identified in LUAD tissues. circEPB41L2 was selected due to its dramatically reduced levels in NSCLC tissues and NSCLC cells. Interestingly, circEPB41L2 blocked glucose uptake, lactate production, NSCLC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, acting as a scaffold, circEPB41L2 bound to the RRM1 domain of the PTBP1 and the E3 ubiquitin ligase TRIP12 to promote TRIP12-mediated PTBP1 polyubiquitylation and degradation, which could be reversed by the HECT domain mutation of TRIP12 and circEPB41L2 depletion. As a result, circEPB41L2-induced PTBP1 inhibition led to PTBP1-induced PKM2 and Vimentin activation but PKM1 and E-cadherin inactivation. These findings highlight the circEPB41L2-dependent mechanism that modulates the "Warburg Effect" and EMT to inhibit NSCLC development and metastasis, offering an inhibitory target for NSCLC treatment.

The impact of induced pluripotent stem cells in animal conservation.

It is widely acknowledged that we are currently facing a critical tipping point with regards to global extinction, with human activities driving us perilously close to the brink of a devastating sixth mass extinction. As a promising option for safeguarding endangered species, induced pluripotent stem cells (iPSCs) hold great potential to aid in the preservation of threatened animal populations. For endangered species, such as the northern white rhinoceros (Ceratotherium simum cottoni), supply of embryos is often limited. After the death of the last male in 2019, only two females remained in the world. IPSC technology offers novel approaches and techniques for obtaining pluripotent stem cells (PSCs) from rare and endangered animal species. Successful generation of iPSCs circumvents several bottlenecks that impede the development of PSCs, including the challenges associated with establishing embryonic stem cells, limited embryo sources and immune rejection following embryo transfer. To provide more opportunities and room for growth in our work on animal welfare, in this paper we will focus on the progress made with iPSC lines derived from endangered and extinct species, exploring their potential applications and limitations in animal welfare research.

Potentially active compounds that improve PAD through angiogenesis: A review.

Peripheral arterial disease (PAD) has been historically neglected, which has resulted in a lack of effective drugs in clinical practice. However, with the increasing prevalence of diseases like atherosclerosis and diabetes, the incidence of PAD is rising and cannot be ignored. Researchers are exploring the potential of promoting angiogenesis through exogenous compounds to improve PAD. This paper focuses on the therapeutic effect of natural products (Salidroside, Astragaloside IV, etc.) and synthetic compounds (Cilostazol, Dapagliflozin, etc.). Specifically, it examines how they can promote autocrine secretion of vascular endothelial cells, enhance cell paracrine interactions, and regulate endothelial progenitor cell function. The activation of these effects may be closely related to PI3K, AMPK, and other pathways. Overall, these exogenous compounds have promising therapeutic potential for PAD. This study aims to summarize the potential active compounds, provide a variety of options for the search for drugs for the treatment of PAD, and bring light to the treatment of patients.

Targeting TRPV1 and TRPA1: A feasible strategy for natural herbal medicines to combat postoperative ileus.

Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.

Hydroxy-α-sanshool from the fruits of Zanthoxylum bungeanum Maxim. promotes browning of white fat by activating TRPV1 to induce PPAR-γ deacetylation.

BACKGROUND: Accumulating evidence suggested increasing energy expenditure is a feasible strategy for combating obesity, and browning of white adipose tissue (WAT) to promote thermogenesis might be one of the attractive ways. Hydroxy-α-sanshool (HAS), a natural amide alkaloid extracted from the fruits of Zanthoxylum bungeanum Maxim, possesses lots of benefits in lipid metabolism regulation. METHODS: The anti-obesity effect of HAS was investigated by establishing an animal model of obesity and a 3T3-L1 differentiation cell model. Effects of HAS on the whole-body fat and liver of obese mice, and the role of HAS in inducing browning of white fat were studied by Micro CT, Metabolic cage detection, Cell mitochondrial pressure detection, transmission electron microscopy and cold exposure assays. Furthermore, the Real-time PCR (qPCR), digital PCR (dPCR), western blot, Co-immunoprecipitation (Co-IP), molecular docking, drug affinity responsive target stability (DARTS), Cellular thermal shift assay (CETSA) and other methods were used to investigate the target and mechanisms of HAS. RESULTS: We found that treatment with HAS helped mice combat obesity caused by a high fat diet (HFD) and improve metabolic characteristics. In addition, our results suggested that the anti-obesity effect of HAS is related to increase energy consumption and thermogenesis via induction of browning of WAT. The further investigations uncovered that HAS can up-regulate UCP-1 expression, increase mitochondria number, and elevate the cellular oxygen consumption rates (OCRs) of white adipocytes. Importantly, the results indicated that browning effects of HAS is closely associated with SIRT1-dependent PPAR-γ deacetylation through activating the TRPV1/AMPK pathway, and TRPV1 is the potential drug target of HAS for the browning effects of WAT. CONCLUSIONS: Our results suggested the HAS can promote browning of WAT via regulating AMPK/SIRT-1/PPARγ signaling, and the potential drug target of HAS is the membrane receptor of TRPV1.

A robust latent CUSUM chart for monitoring customer attrition.

In competitive business, such as insurance and telecommunications, customers can easily replace one provider for another, which leads to customer attrition. Keeping customer attrition rate low is crucial for companies, since retaining a customer is more profitable than recruiting a new one. As a main statistical process control (SPC) method, the CUSUM scheme is able to detect small and persistent shifts in customer attrition. However, customer attrition summaries are typically available on an uneven time scale (e.g. 4-week and 5-week 'business month'), which may not satisfy the assumptions of traditional CUSUM designs. This paper mainly develops a latent CUSUM chart based on an exponential model for monitoring 'monthly' customer attrition, under varying time scales. Both maximum likelihood and least squares methods are studied, where the former mostly performs better and the latter is advantageous for quite small shifts. We apply a Markov chain algorithm to obtain the average run length (ARL), make calibrations for different combinations of parameters, and present reference tables of cutoffs. Three more complicated models are considered to test the robustness of deviations from the initial model. Furthermore, a real example of monitoring monthly customer attrition from a Chinese insurance company is used to illustrate the scheme.

Preclinical Research of Stem Cells: Challenges and Progress.

In recent years, great breakthroughs have been made in basic research and clinical applications of stem cells in regenerative medicine and other fields, which continue to inspire people to explore the field of stem cells. With nearly unlimited self-renewal ability, stem cells can generate at least one type of highly differentiated daughter cell, which provides broad development prospects for the treatment of human organ damage and other diseases. In the field of stem cell research, related technologies for inducing or isolating stem cells are relatively mature, and a variety of stable stem cell lines have been successfully constructed. To realize the full clinical application of stem cells as soon as possible, it is more and more important to further optimize each stage of stem cell research while conforming to Current Good Manufacture Practices (cGMP) standards. Here, we synthesized recent developments in stem cell research and focus on the introduction of xenogenicity in the preclinical research process and the remaining problems of various cell bioreactors. Our goal is to promote the development of technologies for xeno-free culture and clinical expansion of stem cells through in-depth discussion of current research. This review will provide new insight into stem cell research protocols and will contribute to the creation of efficient and stable stem cell expansion systems.

Natural peptides for immunological regulation in cancer therapy: Mechanism, facts and perspectives.

Cancer incidence and mortality rates are increasing annually. Treatment with surgery, chemotherapy and radiation therapy (RT) is unsatisfactory because many patients have advanced disease at the initial diagnosis. However, the emergence of immunotherapy promises to be an effective strategy to improve the outcome of advanced tumors. Immune checkpoint antibodies, which are at the forefront of immunotherapy, have had significant success but still leave some cancer patients without benefit. For more cancer patients to benefit from immunotherapy, it is necessary to find new drugs and combination therapeutic strategies to improve the outcome of advanced cancer patients and achieve long-term tumor control or even eradication. Peptides are promising choices for tumor immunotherapy drugs because they have the advantages of low production cost, high sequence selectivity, high tissue permeability, low toxicity and low immunogenicity etc., and the adjuvant matching and technologies like nanotechnology can further optimize the effects of peptides. In this review, we present the current status and mechanisms of research on peptides targeting multiple immune cells (T cells, natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), regulatory T cells (Tregs)) and immune checkpoints in tumor immunotherapy; and we summarize the current status of research on peptide-based tumor immunotherapy in combination with other therapies including RT, chemotherapy, surgery, targeted therapy, cytokine therapy, adoptive cell therapy (ACT) and cancer vaccines. Finally, we discuss the current status of peptide applications in mRNA vaccine delivery.

Peptide mediated therapy in fibrosis: Mechanisms, advances and prospects.

Fibrosis, a disease characterized by an excess accumulation of extracellular matrix components, could lead to organ failure and death, and is to blame for up to 45 % of all fatalities in developed nations. These disorders all share the common trait of an unchecked and increasing accumulation of fibrotic tissue in the affected organs, which leads to their malfunction and eventual failure, even if their underlying causes are highly diverse and, in some cases, remain unclear. Numerous studies have identified activated myofibroblasts as the common cellular elements ultimately responsible for the replacement of normal tissues with nonfunctional fibrotic tissue. The transforming growth factor-ß pathway, for instance, plays a significant role in practically all kinds of fibrosis. However, there is no specific drug for the treatment of fibrosis, several medications with anti-hepatic fibrosis properties are still in the research and development stages. Peptide, which refers to a substance consisting of 2-50 amino acids, is characterized by structural diversity, low toxicity, biological activities, easy absorption, specific targeting, few side effects, and has been proven to be effective in anti-fibrosis. Here, we summarized various anti-fibrosis peptides in fibrosis including the liver, lungs, kidneys, and other organs. This review will provide a new insight into peptide mediated anti-fibrosis and is helpful to creation of antifibrotic medications.

Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3ß/GS signaling.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia. The fruits of Zanthoxylum bungeanum Maxim. is a common spice and herbal medicine in China, and hydroxy-α-sanshool (HAS) is the most abundant amide in Z. bungeanum and reported to have significant hypoglycemic effects. The purpose of this study was to evaluate the ameliorative effects of HAS on T2DM and the potential mechanisms responsible for those effects. An acute toxicity test revealed the median lethal dose (LD50) of HAS is 73 mg/kg. C57BL/6 J mice were fed a high-fat diet and given an intraperitoneal injection of streptozotocin (STZ) to induce T2DM in mice to evaluate the hypoglycemic effects of HAS. The results showed that HAS significantly reduced fasting blood glucose, reduced pathological changes in the liver and pancreas, and increased liver glycogen content. In addition, glucosamine (GlcN)-induced HepG2 cells were used to establish an insulin resistance cell model and explore the molecular mechanisms of HAS activity. The results demonstrated that HAS significantly increases glucose uptake and glycogen synthesis in HepG2 cells and activates the PI3K/Akt pathway in GlcN-induced cells, as well as increases GSK-3ß phosphorylation, suppresses phosphorylation of glycogen synthase (GS) and increases glycogen synthesis in liver cells. Furthermore, these effects of HAS were blocked by the PI3K inhibitor LY294002. The results of our study suggest that HAS reduces hepatic insulin resistance and increases hepatic glycogen synthesis by activating the PI3K/Akt/GSK-3ß/GS signaling pathway.

Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis.

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.

Sources, Transformations, Syntheses, and Bioactivities of Monoterpene Pyridine Alkaloids and Cyclopenta[c]pyridine Derivatives.

Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of them have a cyclopenta[c]pyridine skeleton. Some compounds containing this structure are potentially bioactive medicinal agents. In this paper, seven drug candidates (A-G), ninety natural source products (1-90), thirty-seven synthesized compounds (91-127), as well as twenty-six key intermediates (S1-S26) were summarized. We categorized five types of MTPAs and one type of cyclopenta[c]pyridine alkaloids in all. Additionally, their possible genetic pathways were proposed. Then, the chemical transformation, biotransformation, chemical synthesis, as well as the bioactivity of MTPAs and cyclopenta[c]pyridine derivatives were analyzed and summarized. Cyclopenta[c]pyridine derivatives can be concisely and chirally synthesized, and they have shown potentials with antibacterial, insecticidal, antiviral, anti-inflammatory, and neuropharmacological activities.

Anti-depression effectiveness of essential oil from the fruits of Zanthoxylum bungeanum maxim. on chronic unpredictable mild stress-induced depression behavior in mice.

The fruits of Zanthoxylum bungeanum Maxim. Was a popular traditional Chinese herbal medicine for pain relief, itching prevention, and diarrhea relief. The fruits of Zanthoxylum bungeanum Maxim. Essential oil (HEO) had an effect of improving anxiety and other emotional disorders. In this paper, we aim to systematically research the antidepressant effects of HEO on Chronic Mild Unpredictable Stimulation (CUMS) mice and explore the relevant molecular mechanisms. Experimental mice were exposed to CUMS for 8 weeks. Meanwhile, for 8 weeks, Sertraline hydrochloride (20 mg/kg/day) and HEO (50, 100, and 150 mg/kg/day) were administered by gavage. HEO treatment increased residence time of central zone in OFT and open-arm in EPM test but decreased immobility times in FST and TST. Moreover, HEO treatment improved the levels of 5-HT, DA, NE, and BDNF, but reduced CRF and CORT levels of the HPA axis in the hippocampus. Network pharmacology predicted the possible mechanisms for the antidepressant effects of HEO by regulation of PI3K/Akt signaling pathway. The mRNA expression of PI3K and Akt were increased, and immunofluorescence results in the hippocampus indicated that HEO treatment could increase the phosphorylation of PI3K and Akt. Besides, the viability of CORT-treated PC12 cells was significantly improved by HEO treatment. The AO-EB staining, MOMP analysis, and flow cytometry analysis results showed HEO inhibiting the CORT-induced apoptosis in PC12 cells significantly. Besides, the phosphorylation of PI3K and Akt in COTR-induced PC12 cells could increase by HEO treatment. In conclusion, HEO ameliorated depression behavior induced by CUMS, potentially via regulating HPA axis and activating PI3K/Akt signaling pathway to reduce neuronal apoptosis.