Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function, and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion, AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which may be related to the promotion of fatty acid oxidation, the reduction of oxidative stress, and the modulation of both the PPAR signaling pathway and pyrimidine metabolism.

Acute kidney injury (AKI) is a prevalent and life-threatening clinical syndrome characterised by a rapid decline in renal function and diverse pathological etiologies. The condition has been demonstrated to be associated with elevated mortality rates and an increased risk of progression to chronic kidney disease. At present, clinicians depend heavily on conventional functional markers, such as serum creatinine and urine output, for the diagnosis and staging of the disease. It is evident that these conventional indicators characteristically manifest a considerable temporal delay and only undergo modification subsequent to considerable tissue damage. This severely restricts the timeframe for early detection and timely therapeutic intervention. Furthermore, standard markers fail to provide specific biological information regarding the underlying cellular injury mechanisms. The utilisation of advanced probe technologies in molecular imaging offers a robust alternative to overcome these inherent diagnostic limitations.This comprehensive review systematically evaluates recent progress in the design and application of two primary categories of molecular imaging tools for acute kidney disease, specifically reactive probes and enzyme-activated probes. Reactive probes are engineered to specifically interact with redox-active chemical species, including hydrogen peroxide, peroxynitrite, hypochlorous acid, and sulfur dioxide. Because oxidative stress constitutes a primary early event in acute renal tubular damage, these probes enable researchers and clinicians to visualize early cellular injury and radical accumulation well before global renal functional decline becomes evident. We discuss the application of these reactive probes across multiple imaging modalities including fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), and photoacoustic techniques. Photoacoustic imaging combines high spatial resolution with deep tissue penetration and has successfully demonstrated the ability to provide diagnostic alerts up to 12 h before any detectable rise in serum creatinine levels. Additionally, specific reactive probes have shown promising translational potential when tested by high-throughput screening in clinical human urine samples. Enzyme-activated probes target the specific catalytic activity of disease-relevant enzymes. These include well-documented renal tubular structural biomarkers such as NAG, GGT, and ALP, along with apoptosis-related caspases and specific nitroreductases. By responding only to enzymatic cleavage, these tools provide highly specific and pathology-directed imaging readouts. Recent structural design strategies in this field have advanced significantly beyond single-enzyme detection. Researchers are now focusing on sophisticated dual-target recognition to minimize background noise, multimodal integration to cross-validate imaging signals, and theranostic applications where probes simultaneously deliver diagnostic feedback and therapeutic agents to injured tissues. Nanotechnology serves as a fundamental enabler for realizing these advanced probe functions. By precisely optimizing nanoparticle parameters such as hydrodynamic size, surface charge, and targeting ligands, researchers can achieve amplified signal output, highly precise kidney delivery, and protection against premature degradation in the systemic circulation. For example, modifying surface charges can significantly enhance the active uptake of nanoprobes by damaged renal tubular epithelial cells.While preclinical probe development has progressed rapidly, moving these technologies into routine clinical practice remains a major challenge. We analyze the translational feasibility and current obstacles from biological, technological, and regulatory perspectives. Although biological targets such as KIM-1, FAP, and ALP have been validated in extensive patient cohorts, practical barriers severely limit their immediate clinical application. These obstacles involve complex changes in in vivo pharmacokinetics. During an acute injury episode, the extreme drop in the glomerular filtration rate alters probe clearance and can cause unwanted systemic accumulation or confusing background imaging signals. Other major hurdles include a lack of comprehensive long-term toxicity data and the absence of standardized manufacturing protocols to ensure batch-to-batch consistency. Future successful translation will require rigorous multi-center clinical studies to confirm the true diagnostic value of these probes over traditional markers. Researchers must also establish strict standardization of imaging procedures and comprehensive safety evaluations. Ultimately, this review provides a thorough reference framework for designing clinically translatable molecular probes and building a precision diagnostic imaging system for acute kidney injury.

Diabetic retinopathy (DR) is one of the most prevalent and vision-threatening microvascular complications of diabetes mellitus, yet its pathogenesis extends far beyond vascular injury alone. As the retina is among the most energy-demanding tissues in the body, its neurons, glial cells, pigment epithelial cells, pericytes, and endothelial cells are highly dependent on mitochondrial oxidative phosphorylation to maintain visual signal transduction, ionic homeostasis, and neurovascular integrity. This review summarizes current evidence indicating that mitochondrial dysfunction is not merely a downstream consequence of chronic hyperglycemia, but a central pathogenic hub that initiates, amplifies, and perpetuates retinal neurovascular degeneration in DR. Persistent hyperglycemia activates multiple abnormal metabolic pathways, including the polyol pathway, hexosamine pathway, protein kinase C signaling, advanced glycation end-product formation, and angiotensin II-related responses. Although these pathways differ mechanistically, they converge on excessive reactive oxygen species (ROS) generation, antioxidant depletion, and mitochondrial injury. Under diabetic stress, electron transport chain overload promotes mitochondrial ROS leakage, damages mitochondrial DNA, disrupts membrane potential, and impairs the transcription of key respiratory chain components. In parallel, mitochondrial quality-control systems become progressively compromised. The balance between fusion and fission shifts toward pathological fragmentation through reduced MFN1/2 and OPA1 activity and enhanced DRP1-mediated fission. Mitochondrial biogenesis is suppressed through inhibition of the AMPK/SIRT1/PGC-1α/NRF1/TFAM axis, while mitophagy changes from an early compensatory response to a later state of autophagic flux blockade and accumulation of dysfunctional mitochondria. Importantly, damaged mitochondria serve as signal amplifiers linking metabolic stress to inflammation and programmed cell death. Mitochondrial ROS, oxidized mitochondrial DNA, calcium overload, cardiolipin exposure, and membrane permeabilization activate interrelated death pathways, including intrinsic apoptosis, ferroptosis, and pyroptosis. Cytochrome C and apoptosis-inducing factor promote caspase-dependent and caspase-independent apoptosis; iron dyshomeostasis, glutathione depletion, GPX4 dysfunction, and lipid peroxidation drive ferroptosis; and mitochondrial danger signals activate the NLRP3 inflammasome and gasdermin-dependent pyroptosis. These pathways jointly damage the retinal neurovascular unit and contribute to pericyte loss, endothelial barrier breakdown, Müller cell dysfunction, retinal ganglion cell apoptosis, retinal pigment epithelial injury, and photoreceptor degeneration. This review also emphasizes the role of epigenetic regulation in stabilizing mitochondrial pathology. DNA methylation, histone modifications, and non-coding RNAs interact to silence mitochondrial protective genes, alter antioxidant responses, and maintain the “metabolic memory” of DR even after glycemic normalization. Therefore, mitochondrial dysfunction should be understood as a dynamic, multidimensional network rather than a single pathological event. Current clinical approaches, such as laser photocoagulation, intravitreal anti-VEGF therapy, and vitrectomy, mainly target advanced vascular lesions and are limited by invasiveness, incomplete responsiveness, recurrence, and potential adverse effects. Therapeutically, strategies targeting mitochondrial ROS, restoring mitochondrial dynamics, enhancing biogenesis, regulating mitophagy, inhibiting inflammasome activation, correcting epigenetic abnormalities, and improving targeted delivery systems show promising potential. However, major translational barriers remain, including retinal cell heterogeneity, stage-specific mitochondrial responses, insufficient organelle-specific drug delivery, and long-term safety concerns. A deeper understanding of mitochondrial regulatory networks may support earlier, more precise, and multi-target interventions for preventing or slowing DR progression.

Objective: To investigate the characteristics of public health emergencies in Jinhua City, Zhejiang Province from 2014 to 2023, so as to provide the reference for prevention and control of public health emergencies. Methods: Data of public health emergencies and related information in Jinhua City from 2014 to 2023 were collected through Emergency Public Reporting System of Chinese Disease Prevention and Control Information System. Attack rates, and distribution of time, areas and places were descriptively analyzed. Results: A total of 276 public health emergencies were reported in Jinhua City from 2014 to 2023. There were 10 324 reported cases and 7 deaths, with an attack rate of 0.32%. There were 53 Ⅳ-level (19.20%) and 223 unclassified public health emergencies (80.80%). Infectious disease emergencies were predominant types, accounting for 97.83% (270 events). The three most common infectious disease emergencies were other infectious diarrhea (42.03%), influenza (21.01%) and COVID-19 (16.30%). The reported public health emergencies peaked in November and December, with 66 and 45 events reported, respectively. The three most counties (cities, districts) included Yiwu City, Wucheng District and Lanxi City, accounting for 24.28% (67 events), 18.48% (51 events) and 11.96% (33 events), respectively. School and preschool institutions were predominant places where public health emergencies occurred (198 events, 71.74%). Conclusions The public health emergencies in Jinhua City from 2014 to 2023 were Ⅳ-level and unclassified emergencies, and infectious disease emergencies were predominant. November and December were the peak reporting periods, and schools and preschool institutions were the main places where these events occurred.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: Iron deposition plays a crucial role in the pathophysiology of Parkinson's disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). METHODS: A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2 * and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. RESULTS: Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata ( P <0.001) and compacta ( P <0.001), SN ( P <0.001), red nucleus (RN, P <0.001), globus pallidus ( P <0.001), putamen (PUT, P = 0.021), and thalamus ( P = 0.029) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT ( P <0.001), RN ( P = 0.003), SN ( P = 0.017), and caudate nucleus ( P = 0.017) than MSA patients, and lower iron content in RN ( P = 0.001), PUT ( P <0.001), globus pallidus ( P = 0.004), SN ( P = 0.015), and caudate nucleus ( P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.86). CONCLUSIONS: Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. REGISTRISION PROSPERO (CRD42022344413).
Humans ; Parkinson Disease/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Iron/metabolism*

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Moringa oleifera, widely utilized in Ayurvedic medicine, is recognized for its leaves, seeds, and velamen possessing traditional effects such as vātahara(wind alleviation), sirovirecaka(brain clearing), and hridya(mental nourishment). This study aims to identify the medicinal part of ■ in the Sārasvata ghee formulation as described in the Bower Manuscript, while investigating the ameliorative effects of different medicinal parts of M. oleifera on learning and memory deficits in mice and elucidating the underlying molecular mechanisms. A total of 144 male ICR mice were randomly assigned to the following groups: control, model(scopolamine hydrobromide, Sco, 2 mg·kg~(-1)), donepezil(donepezil hydrochloride, Don, 3 mg·kg~(-1)), M. oleifera leaf low-, medium-, and high-dose groups(0.5, 1, 2 g·kg~(-1)), M. oleifera seeds low-, medium-, and high-dose groups(0.25, 0.5, 1 g·kg~(-1)), and M. oleifera velamen low-, medium-, and high-dose groups(0.31, 0.62, 1.24 g·kg~(-1)). Learning and memory abilities were assessed using the passive avoidance test and Morris water maze. Nissl and HE staining were employed to examine histopathological changes in the hippocampus. Transcriptomics and targeted metabolomics were used to screen differential genes and metabolites, with MetaboAnalyst 6.0 and O2PLS methods applied to identify key disease-related targets and pathways. RESULTS:: demonstrated that M. oleifera leaf(1 g·kg~(-1)) significantly ameliorated Sco-induced learning and memory deficits, outperforming M. oleifera seeds(0.25 g·kg~(-1)) and M. oleifera velamen(1.24 g·kg~(-1)). This was evidenced by improved behavioral performance, reversal of neuronal damage, and reduced acetylcholinesterase(AChE) activity. Multi-omics analysis revealed that M. oleifera leaf upregulated Tuba1c gene expression through the synaptic vesicle cycle, enhancing glutamate(Glu), dopamine(DA), and acetylcholine(ACh) release via Tuba1c-Glu associations for neuroprotection. M. oleifera seeds targeted the dopaminergic synapse pathway, promoting memory consolidation through Drd2-ACh associations. M. oleifera velamen was associated with the cocaine addiction pathway, modulating dopamine metabolism via Adora2a-DOPAC, with limited relevance to learning and memory. In conclusion, M. oleifera leaf exhibits superior efficacy and mechanistic advantages over M. oleifera seeds and velamen, suggesting that the ■ in the Sārasvata ghee formulation is likely M. oleifera leaf, providing scientific evidence for its identification in ancient texts.
Animals ; Moringa oleifera/chemistry* ; Male ; Mice ; Seeds/chemistry* ; Plant Leaves/chemistry* ; Mice, Inbred ICR ; Memory Disorders/psychology* ; Transcriptome/drug effects* ; Memory/drug effects* ; Learning/drug effects* ; Metabolomics ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Maze Learning/drug effects*