Copper-catalyzed oxidative cyclization of 2-(1H-pyrrol-1-yl)aniline and alkylsilyl peroxides: a route to pyrrolo[1,2-a]quinoxalines.

An efficient method was developed for the one-pot construction of pyrrolo[1,2-a]quinoxalines via a Cu(II)-catalyzed domino reaction between 2-(1H-pyrrol-1-yl)anilines and alkylsilyl peroxides. This reaction proceeds through C-C bond cleavage and new C-C and C-N bond formation. A mechanistic study suggests that alkyl radical species participate in the cascade reaction.

Electrochemical oxidative dehydrogenative annulation of 1-(2-aminophenyl)pyrroles with cleavage of ethers to synthesize pyrrolo[1,2-a]quinoxaline derivatives.

An array of pyrrolo[1,2-a]quinoxaline derivatives were achieved with moderate to good yields via the electrochemical redox reaction, which includes the functionalization of C(sp3)-H bonds and the construction of C-C and C-N bonds. In this atom economic reaction, THF was used as both a reactant and a solvent, and H2 was the sole by-product.

HDAC inhibitors as a potential therapy for chemotherapy-induced neuropathic pain.

Cancer, a chronic disease characterized by uncontrolled cell development, kills millions of people globally. The WHO reported over 10 million cancer deaths in 2020. Anticancer medications destroy healthy and malignant cells. Cancer treatment induces neuropathy. Anticancer drugs cause harm to spinal cord, brain, and peripheral nerve somatosensory neurons, causing chemotherapy-induced neuropathic pain. The chemotherapy-induced mechanisms underlying neuropathic pain are not fully understood. However, neuroinflammation has been identified as one of the various pathways associated with the onset of chemotherapy-induced neuropathic pain. The neuroinflammatory processes may exhibit varying characteristics based on the specific type of anticancer treatment delivered. Neuroinflammatory characteristics have been observed in the spinal cord, where microglia and astrocytes have a significant impact on the development of chemotherapy-induced peripheral neuropathy. The patient's quality of life might be affected by sensory deprivation, loss of consciousness, paralysis, and severe disability. High cancer rates and ineffective treatments are associated with this disease. Recently, histone deacetylases have become a novel treatment target for chemotherapy-induced neuropathic pain. Chemotherapy-induced neuropathic pain may be treated with histone deacetylase inhibitors. Histone deacetylase inhibitors may be a promising therapeutic treatment for chemotherapy-induced neuropathic pain. Common chemotherapeutic drugs, mechanisms, therapeutic treatments for neuropathic pain, and histone deacetylase and its inhibitors in chemotherapy-induced neuropathic pain are covered in this paper. We propose that histone deacetylase inhibitors may treat several aspects of chemotherapy-induced neuropathic pain, and identifying these inhibitors as potentially unique treatments is crucial to the development of various chemotherapeutic combination treatments.

Buchwald-Hartwig Amination of Coordinating Heterocycles Enabled by Large-but-Flexible Pd-BIAN-NHC Catalysts.

A new class of large-but-flexible Pd-BIAN-NHC catalysts (BIAN=acenaphthoimidazolylidene, NHC=N-heterocyclic carbene) has been rationally designed to enable the challenging Buchwald-Hartwig amination of coordinating heterocycles. This robust class of BIAN-NHC catalysts permits cross-coupling under practical aerobic conditions of a variety of heterocycles with aryl, alkyl, and heteroarylamines, including historically challenging oxazoles and thiazoles as well as electron-deficient heterocycles containing multiple heteroatoms with BIAN-INon (N,N'-bis(2,6-di(4-heptyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-8-ylidene) as the most effective ligand. Studies on the ligand structure and electronic properties of the carbene center are reported. The study should facilitate the discovery of even more active catalyst systems based on the unique BIAN-NHC scaffold.

Ruthenium(II) complexes with N-heterocyclic carbene-phosphine ligands for the N-alkylation of amines with alcohols.

Metal hydride complexes are key intermediates for N-alkylation of amines with alcohols by the borrowing hydrogen/hydrogen autotransfer (BH/HA) strategy. Reactivity tuning of metal hydride complexes could adjust the dehydrogenation of alcohols and the hydrogenation of imines. Herein we report ruthenium(ii) complexes with hetero-bidentate N-heterocyclic carbene (NHC)-phosphine ligands, which realize smart pathway selection in the N-alkylated reaction via reactivity tuning of [Ru-H] species by hetero-bidentate ligands. In particular, complex 6cb with a phenyl wingtip group and BArF- counter anion, is shown to be one of the most efficient pre-catalysts for this transformation (temperature is as low as 70 °C, neat conditions and catalyst loading is as low as 0.25 mol%). A large variety of (hetero)aromatic amines and primary alcohols were efficiently converted into mono-N-alkylated amines in good to excellent isolated yields. Notably, aliphatic amines, challenging methanol and diamines could also be transformed into the desired products. Detailed control experiments and density functional theory (DFT) calculations provide insights to understand the mechanism and the smart pathway selection via [Ru-H] species in this process.

Glycosides for Peripheral Neuropathic Pain: A Potential Medicinal Components.

Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.

Echinacoside Alleviates Hypoxic-Ischemic Brain Injury in Neonatal Rat by Enhancing Antioxidant Capacity and Inhibiting Apoptosis.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of death and disability in neonatal or perinatal all over the world, seriously affecting children, families and society. Unfortunately, only few satisfactory therapeutic strategies have been developed. It has been demonstrated that Echinacoside (ECH), the major active component of Cistanches Herba, exerts many beneficial effects, including antioxidative, anti-apoptosis, and neuroprotective in the traditional medical practice in China. Previous research has demonstrated that ECH plays a protective effect on ischemic brain injury. This study aimed to investigate whether ECH provides neuroprotection against HIBD in neonatal rats. We subjected 120 seven-day-old Sprague-Dawley rats to cerebral hypoxia-ischemia (HI) and randomly divided into the following groups: sham group, HI group and ECH (40, 80 and 160 mg/kg, intraperitoneal) post-administration group. After 48 h of HI, 2,3,5-Triphenyltetrazolium chloride, Hematoxylin-Eosin and Nissl staining were conducted to evaluate the extent of brain damage. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) production were assessed to determine the antioxidant capacity of ECH. TUNEL staining and Western blot analysis was performed to respectively estimate the extent of brain cell apoptosis and the expression level of the apoptosis-related proteins caspase-3, Bax, and Bcl-2. Results showed that ECH remarkably reduced the brain infarct volume and ameliorated the histopathological damage to neurons. ECH post-administration helped recovering the antioxidant enzyme activities and decreasing the MDA production. Furthermore, ECH treatment suppressed neuronal apoptosis in the rats with HIBD was by reduced TUNEL-positive neurons, the caspase-3 levels and increased the Bcl-2/Bax ratio. These results suggested that ECH treatment was beneficial to reducing neuronal damage by attenuating oxidative stress and apoptosis in the brain under HIBD.

Flexible Steric Bulky Bis(Imino)acenaphthene (BIAN)-Supported N-Heterocyclic Carbene Palladium Precatalysts: Catalytic Application in Buchwald-Hartwig Amination in Air.

To achieve efficient palladium-catalyzed cross-coupling reaction under mild reaction conditions with the flexible steric bulk strategy, a series of Pd-PEPPSI (PEPPSI: pyridine-enhanced precatalyst preparation, stabilization, and initiation) complexes C1-C6 were synthesized and characterized, in which unsymmetric flexible steric bulk was introduced on the N-aryl of ancenaphthyl skeleton. These well-defined palladium complexes were found to be excellent precatalysts for Buchwald-Hartwig amination of aryl chlorides with amines in air. The electronic effect of the Pd-PEPPSI complexes and the effect of ancillary pyridine ligands were evaluated, among which complex C3 exhibited the most efficiency. It was demonstrated that the cross-coupling products were obtained in excellent yields in the presence of 0.5-0.1 mol % palladium loading. A wide range of aryl- and heteroaryl chlorides as well as various amines were compatible. The oxidative addition of aryl chlorides is revealed to be the rate-determining step in the catalytic cycle. The catalytic activity can be enhanced by introducing electron-donating groups to the Pd-PEPPSI complexes. This type of Pd-PEPPSI precatalyst showed the most efficiency reported to date for the challenging C-N cross-coupling reactions requiring no anhydrous and inert atmosphere protections, suggesting flexible steric bulk as a promising catalyst design strategy.

An Intermolecular Hydroarylation of Unactivated Arylcyclopropane via Re2O7/HFIP-Mediated Ring Opening.

In this paper, we describe a Re2O7-mediated ring-opening arylation of unactivated arylcyclopropane because of its functionalization with various arenes via Friedel-Crafts-type reactivity. This protocol allows facile access to functionalized 1,1-diaryl alkanes and is characterized by a broad substrate scope, mild reaction conditions, high efficiency, and high atom economy. Both density functional theory calculations and deuterium labeling experiments were carried out to justify the indispensable role of HFIP in this transformation and pointed to Re2O7-mediated ring opening being the rate-determining step.

Neuroprotective effects of oxymatrine on hypoxic-ischemic brain damage in neonatal rats by activating the Wnt/ß-catenin pathway.

Neuronal apoptosis is a major pathological process associated with neurological dysfunction in neonates after hypoxic-ischemic brain damage (HIBD). Our previous study demonstrated that oxymatrine (OMT) exerts potential neuroprotective effects on neonatal rats subjected to hypoxic-ischemic insult. However, the underlying molecular mechanism remains unclear. In this study, we investigated the effects of OMT-mediated neuroprotection on neonatal HIBD by attempting to determine its effect on the Wnt/ß-catenin signaling pathway and explored the underlying mechanism. Both 7-day-old rat pups and primary hippocampus neurons were used to establish the HIBD and oxygen-glucose deprivation (OGD) injury models, respectively. Our results demonstrated that OMT treatment significantly increased cerebral blood flow and reduced S100B concentration, infarct volume, and neuronal apoptosis in neonatal rats. In vitro, OMT markedly increased cell viability and MMP level and decreased DNA damage. Moreover, OMT improved the mRNA and protein levels of Wnt1 and ß-catenin, inhibited the expression of DKK1 and GSK-3ß, enhanced the nuclear transfer of ß-catenin, and promoted the binding activity of ß-catenin with Tcf-4; however, it downregulated the expression of cleaved caspase-3 and cleaved caspase-9. Notably, the introduction of XAV-939 (a Wnt/ß-catenin signaling inhibitor) reversed the positive effects of OMT both in vivo and in vitro. Collectively, our findings demonstrated that OMT exerted a neuroprotective effect on neonatal HIBD by inhibiting neuronal apoptosis, which was partly via the activation of the Wnt/ß-catenin signaling pathway.

Neuroprotective strategies for neonatal hypoxic-ischemic brain damage: Current status and challenges.

Neonatal hypoxic-ischemic brain damage (HIBD) is a prominent contributor to both immediate mortality and long-term impairment in newborns. The elusive nature of the underlying mechanisms responsible for neonatal HIBD presents a significant obstacle in the effective clinical application of numerous pharmaceutical interventions. This comprehensive review aims to concentrate on the potential neuroprotective agents that have demonstrated efficacy in addressing various pathogenic factors associated with neonatal HIBD, encompassing oxidative stress, calcium overload, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory response, and apoptosis. In this review, we conducted an analysis of the precise molecular pathways by which these drugs elicit neuroprotective effects in animal models of neonatal hypoxic-ischemic brain injury (HIBD). Our objective was to provide a comprehensive overview of potential neuroprotective agents for the treatment of neonatal HIBD in animal experiments, with the ultimate goal of enhancing the feasibility of clinical translation and establishing a solid theoretical foundation for the clinical management of neonatal HIBD.

Protective effects of leonurine hydrochloride on pyroptosis in premature ovarian insufficiency via regulating NLRP3/GSDMD pathway.

BACKGROUND: Premature ovarian insufficiency is common in clinically infertile patients. The NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Gasdermin D (GSDMD) signaling pathway plays a key role in premature ovarian insufficiency. Leonurine (Leo) is one of the important active ingredients extracted from Leonurus japonicus Houttuyn, which can inhibit NLRP3 activation. However, whether leonurine hydrochloride plays a protective role in premature ovarian insufficiency through actions on NLRP3/GSDMD signaling is not yet known. METHODS: After cyclophosphamide-induced premature ovarian insufficiency was established in female mice, Leo was injected intraperitoneally over four weeks to evaluate the ovarian function and anti-pyroptosis effects using the metrics of fertility, serum hormone level, ovary weight, follicle number, expression of NLRP3/GSDMD pathway-related proteins, and serum IL-18 and IL-1ß levels. RESULTS: Intraperitoneal administration of leonurine hydrochloride was found to significantly protect fertility and maintain both serum hormone levels and follicle number in mice with premature ovarian insufficiency. Mice treated with leonurine hydrochloride consistently resisted cyclophosphamide-induced ovarian damage by inhibiting the activation of NLRP3 inflammasome, Caspase-1 and GSDMD in both ovarian tissue and granulosa cells, which led to lower levels of IL-18 and IL-1ß in the serum (p < 0.05, p < 0.01, p < 0.001). CONCLUSION: Intraperitoneal administration of leonurine hydrochloride prevents cyclophosphamide-induced premature ovarian insufficiency in mice by inhibiting NLRP3/GSDMD-mediated pyroptosis.

Targeting the chemokine ligand 2-chemokine receptor 2 axis provides the possibility of immunotherapy in chronic pain.

Chronic pain affects patients' physical and psychological health and quality of life, entailing a tremendous public health challenge. Currently, drugs for chronic pain are usually associated with a large number of side effects and poor efficacy. Chemokines in the neuroimmune interface combine with their receptors to regulate inflammation or mediate neuroinflammation in the peripheral and central nervous system. Targeting chemokines and their receptor-mediated neuroinflammation is an effective means to treat chronic pain. In recent years, growing evidence has shown that the expression of chemokine ligand 2 (CCL2) and its main chemokine receptor 2 (CCR2) is involved in its occurrence, development and maintenance of chronic pain. This paper summarises the relationship between the chemokine system, CCL2/CCR2 axis, and chronic pain, and the CCL2/CCR2 axis changes under different chronic pain conditions. Targeting chemokine CCL2 and its chemokine receptor CCR2 through siRNA, blocking antibodies, or small molecule antagonists may provide new therapeutic possibilities for managing chronic pain.

Antinociceptive and neuroprotective effect of echinacoside on peripheral neuropathic pain in mice through inhibiting P2X7R/FKN/CX3CR1 pathway.

Clinically, neuropathic pain treatment remains a challenging issue because the major therapy, centred around pharmacological intervention, is not satisfactory enough to patient by reason of low effectiveness and more adverse reaction. Therefore, it is still necessary to find more effective and safe therapy to ameliorate neuropathic pain. The purpose of this study was to explore the antinociceptive effect of Echinacoside (ECH), an active compound of Cistanche deserticola Ma, on peripheral neuropathic pain induced by chronic constriction injury (CCI) in mice, and to demonstrate its potential mechanism in vivo and vitro. In the present study, results showed that intraperitoneal administration of ECH (50, 100, and 200 mg/kg) could alleviate mechanical allodynia, cold allodynia and thermal hyperalgesia via behavioural test. Moreover, the structure and function of injured sciatic nerve by CCI were taken a turn for the better to a certain extent after ECH treatment using histopathological and electrophysiological test. Furthermore, ECH repressed the expression of the P2X7R and FKN and reduced the expression and release of the IL-1ß, IL-6 and TNF-α. Besides, ECH could decrease Ca2+ influx and Cats efflux and inhibit phosphorylation of p38MAPK. To sum up, the present study illustrated that ECH could alleviate peripheral neuropathic pain by inhibiting microglia overactivation and inflammation through P2X7R/FKN/CX3CR1 signalling pathway in spinal cord. This study would provide a new perspective and strategy for the pharmacological treatment on neuropathic pain.

Hippocampal Proteomic Analysis in Male Mice Following Aggressive Behavior Induced by Long-Term Administration of Perampanel.

Antiepileptic drugs have been shown to be associated with inducing or exacerbating adverse psychotropic reaction, including aggressive behavior. Perampanel, the first pharmacological compound approved by the FDA in 2012, is an effective antiepileptic drug for intractable epilepsy but induces severe aggression. So far, the underlying molecular mechanisms of aggression induced by perampanel remain incompletely understood. In the present study, a model of aggressive behavior based on the clinical use of perampanel was established and resident-intruder test and open field test were performed. Changes in hippocampal protein profiles were detected by tandem mass tag (TMT) proteomics. The behavioral results indicated that long-term use of perampanel increased the aggressive behavior of C57BL/6J mice. Proteomic analysis revealed that 93 proteins were significantly altered in the hippocampus of the perampanel-treated group (corrected p < 0.05), which were divided into multiple functional groups, mainly related to synaptic function, synaptogenesis, postsynaptic density protein, neurite outgrowth, AMPA-type glutamate receptor immobilization, and others. Bioinformatic analysis showed that differentially expressed proteins were involved in synaptic plasticity and the Ras signaling pathway. Furthermore, validation results by western blot demonstrated that glutamate receptor 1 (GluA1) and phosphorylation of mitogen-activated protein kinase (ERK1/2) were notably up-regulated, and synaptophysin (Syn) and postsynaptic density 95 (PSD95) were down-regulated in perampanel-treated mice. Therefore, our results provide valuable insight into the molecular mechanisms of aggressive behavior induced by perampanel, as well as potential options for safety treatment of perampanel in the future.

Koumine regulates macrophage M1/M2 polarization via TSPO, alleviating sepsis-associated liver injury in mice.

BACKGROUND: Translocator protein (TSPO) is an 18-kDa transmembrane protein found primarily in the mitochondrial outer membrane, and it is implicated in inflammatory responses, such as cytokine release. Koumine (KM) is an indole alkaloid extracted from Gelsemium elegans Benth. It has been reported to be a high-affinity ligand of TSPO and to exert anti-inflammatory and immunomodulatory effects in our recent studies. However, the protective effect of KM on sepsis-associated liver injury (SALI) and its mechanisms are unknown. PURPOSE: To explore the role of TSPO in SALI and then further explore the protective effect and mechanism of KM on SALI. METHODS: The effect of KM on the survival rate of septic mice was confirmed in mouse models of caecal ligation and puncture (CLP)-induced and lipopolysaccharide (LPS)-induced sepsis. The protective effect of KM on CLP-induced SALI was comprehensively evaluated by observing the morphology of the mouse liver and measuring liver injury markers. The serum cytokine content was detected in mice by flow cytometry. Macrophage polarization in the liver was examined using western blotting. TSPO knockout mice were used to explore the role of TSPO in sepsis liver injury and verify the protective effect of KM on sepsis liver injury through TSPO. RESULTS: KM significantly improved the survival rate of both LPS- and CLP-induced sepsis in mice. KM has a significant liver protective effect on CLP-induced sepsis in mice. KM treatment ameliorated liver ischaemia, improved liver pathological injuries, and decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and proinflammatory cytokines in serum. Western blotting results showed that KM inhibited M1 polarization of macrophages and promoted M2 polarization. In TSPO knockout mice, we found that TSPO knockout can improve the survival rate of septic mice, ameliorate liver ischaemia, improve liver pathological injuries, and decrease the levels of ALT, AST, and LDH. In addition, TSPO knockout inhibits the M1 polarization of macrophages in the liver of septic mice and promotes M2 polarization and the serum levels of proinflammatory cytokines. Interestingly, in TSPO knockout septic mice, these protective effects of KM were no longer effective. CONCLUSIONS: We report for the first time that TSPO plays a critical role in sepsis-associated liver injury by regulating the polarization of liver macrophages and reducing the inflammatory response. KM, a TSPO ligand, is a potentially desirable candidate for the treatment of SALI that may regulate macrophage M1/M2 polarization through TSPO in the liver.

Geniposide attenuates spermatogenic dysfunction via inhibiting endoplasmic reticulum stress in male mice.

BACKGROUND: Spermatogenesis dysfunction is common in clinically infertile patients. Geniposide (GP) is one of the important active ingredients extracted from Eucommia ulmoides. However, the protective effect and mechanism of GP in the treatment of spermatogenic dysfunction is not known yet. METHODS: After cyclophosphamide-induced spermatogenic dysfunction was established in male mice, we gavaged GP for 4 weeks to evaluate spermatogenic function and anti-apoptotic effects by fertility, testicular weight, sperm quality, endoplasmic reticulum stress (ER stress), comet assay and serum testosterone level. RESULTS: GP can improve the damage of fertility and reproductive organs induced by cyclophosphamide and increase the number and activity of sperm. In comet assay, it was found that GP administration could alleviate sperm DNA damage induced by cyclophosphamide. In addition, GP treatment can significantly reduce ThT fluorescence intensity and improve endoplasmic reticulum stress induced by cyclophosphamide. Besides, TUNEL staining and WB showed that GP could inhibit the excessive apoptosis of cells and protect testis. (p < 0.05, p < 0.01, p < 0.001). CONCLUSION: The protective effect of Geniposide on cyclophosphamide-induced spermatogenic dysfunction in mice is related to the inhibition of endoplasmic reticulum stress.

Development of protective agents against ovarian injury caused by chemotherapeutic drugs.

BACKGROUND: Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant, preventing chemotherapy-induced ovarian injury will often possess even more significant benefits. OBJECTIVE: We aimed at demonstrating the hazardous effects and mechanisms of ovarian injury by chemotherapeutic agents, as well as demonstrating agents that protect the ovary from chemotherapy-induced injury. RESULTS: Chemotherapeutic agents cause death or accelerate activation of follicles and damage to the blood vessels in the ovary, resulting in inflammation. These often require drug development to protect the ovaries from injury. CONCLUSIONS: Our findings provide a basis for the development of drugs to protect the ovaries from injury. Although there are many preclinical studies on potential protective drugs, there is still an urgent need for a large number of clinical experiments to verify their potential use.

Tungsten-Catalyzed Direct N-Alkylation of Anilines with Alcohols.

The implementation of non-noble metals mediated chemistry is a major goal in homogeneous catalysis. Borrowing hydrogen/hydrogen autotransfer (BH/HA) reaction, as a straightforward and sustainable synthetic method, has attracted considerable attention in the development of non-noble metal catalysts. Herein, we report a tungsten-catalyzed N-alkylation reaction of anilines with primary alcohols via BH/HA. This phosphine-free W(phen)(CO)4 (phen=1,10-phenthroline) system was demonstrated as a practical and easily accessible in-situ catalysis for a broad range of amines and alcohols (up to 49 examples, including 16 previously undisclosed products). Notably, this tungsten system can tolerate numerous functional groups, especially the challenging substrates with sterically hindered substituents, or heteroatoms. Mechanistic insights based on experimental and computational studies are also provided.

Neuroprotective Effects of Oxymatrine on PI3K/Akt/mTOR Pathway After Hypoxic-Ischemic Brain Damage in Neonatal Rats.

Oxymatrine (OMT), a quinolizidine alkaloid extracted from traditional Chinese herb Sophora flavescens Ait, has drawn attention because of its beneficial bioactivities against hypoxic-ischemic brain damage (HIBD). However, the underlying molecular mechanism remains unclear. In this study, we determined the in vivo and in vitro effects of OMT on seven-day old Sprague-Dawley rats with HIBD and in a rat model of primary hippocampal neuron oxygen glucose deprivation reoxygenation (OGD/R). This study was aimed to evaluate whether OMT exerted neuroprotective effects mediated by the (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin) PI3K/Akt/mTOR pathway after HIBD. Experimental results showed that the alkaloid significantly improved the early neurofunctional development, brain water content, abnormal pathological changes, and necrosis of neurons after HIBD. Moreover, OMT enhanced the cell viability and stabilized the mitochondrial permeability transition pore in the primary hippocampal neurons after OGD/R. OMT significantly decreased the autophagosome generation, elevated the expression of PI3K, Akt, and mTOR, and simultaneously reversed the mRNA expression of microtubule-associated protein 1-light chain 3 (LC3), Beclin-1, and sequestosomel (P62) induced by hypoxia and ischemia. However, these protective effects against HIBD could be suppressed when rapamycin, a specific inhibitor of mTOR, was included. Hence, the OMT exerted neuroprotective effects against HIBD by attenuating excessive autophagy by mediating the PI3K/Akt/mTOR pathway.