Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Aromatic immunity in traditional Chinese medicine(TCM) is the medical knowledge accumulated in the process of people's struggling with diseases. It plays an important role in plague prevention, disease treatment, health preservation, and rehabilitation, and has profound TCM basic theoretical support and abundant modern scientific evidence. With the in-depth promotion of the Healthy China initiative and the succession of health needs in the post-COVID-19 era, how to practice the health concept of aromatic immunity in TCM and develop its health service resources with high quality has become an important proposition to be discussed urgently. This paper summarizes the cognitive process, puts forward the basic concept, discusses the scientific connotation and clinical application value, and looks forward to the future development trend of aromatic immunity in TCM, aiming to provide guidance for the development of great health products and promote the application of aromatic immunity in TCM in serving people's health.
Medicine, Chinese Traditional/methods* ; Humans ; COVID-19/immunology* ; China ; Drugs, Chinese Herbal/therapeutic use* ; SARS-CoV-2

Aromatic traditional Chinese medicine(TCM) has played an important role against epidemics and viruses, and volatile components are the main components that exert the pharmacological effects of aromatic TCM. By screening the related monomer components in aromatic TCM against epidemic and viruses and analyzing and endowing TCM with medicinal properties based on its clinical application and pharmacological research according to the theoretical thinking of TCM, the key technical issues of compatibility of TCM monomer components were solved from a theoretical perspective, providing new ideas and methods for screening raw materials and formulas for the development of new TCM drugs. Based on the conditions of antiviral activity, clinical application foundation, definite therapeutic effect, and high safety, a gradient screening of aromatic TCM was carried out. Firstly, 30 aromatic TCM were screened from anti-epidemic literature and clinical trial formulas, and seven volatile monomers were further screened from them. Then, four monomer components with significant effects, namely patchouli alcohol, carvacrol, p-cymene, and eucalyptol were screened. By adopting the "four-step method for a systematic study of TCM properties", the four monomer components were endowed with medicinal properties, and compatibility and combination studies were conducted to explore the theoretical basis of monomer formulas and form monomer formulas guided by TCM theory. The screening results of volatile monomers in aromatic TCM against viral pneumonia included patchouli alcohol, carvacrol, p-cymene, and eucalyptol. The medicinal properties and compatibility theory of volatile monomer components in TCM were explored. Patchouli alcohol was the main herb, with a cool and pungent nature. It entered the lung meridian to dispel evil Qi and has the effects of aromatization, detoxification, and epidemic prevention. Carvacrol was a minister drug with a cool and pungent taste. It had the effects of aromatizing, moistening, and dissolving the exterior, as well as strengthening the spleen and stomach. p-Cymene was an adjunctive medicine with a mild and pungent nature. It entered the lungs and kidneys and had the effects of aromatic purification, cough relief, and asthma relief. Eucalyptol was also an adjunctive medicine with a pungent and warm taste. It had the functions of aromatic purification, cough relief, phlegm reduction, and pain relief. The combination of the four medicines had the effects of aromatizing, moistening, detoxifying, and epidemic prevention, as well as relieving cough and asthma and strengthening the spleen and stomach. They were used to treat viral pneumonia caused by upper respiratory tract viral infections, with symptoms such as chest tightness, cough, wheezing, fatigue, nasal congestion, runny nose, nausea, and vomiting. This study has laid a literature and theoretical foundation for further drug efficacy verification experiments, compatibility efficacy experiments, and subsequent product development and clinical applications, and it serves as an innovative practice that combines literature research, theoretical research, experimental research, and clinical practice to develop new products.
Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/pharmacology* ; Humans ; Pneumonia, Viral/virology* ; Medicine, Chinese Traditional ; Volatile Organic Compounds/pharmacology* ; Animals

This paper aims to investigate the influence of eucalyptol on the biological effects of spleen cold and spleen heat syndromes in rats and its regulation of transient receptor potential vanilloid 1(TRPV1), transient receptor potential melastatin 8(TRPM8), and uncoupling protein 1(UCP1), so as to explore the cold-heat properties of eucalyptol. Rats were randomly divided into groups as follows: blank group, spleen cold syndrome model group, spleen cold syndrome+Atractylodis Rhizoma group, spleen cold syndrome + low-dose eucalyptol group, and spleen cold syndrome+high-dose eucalyptol group, as well as blank group, spleen heat syndrome model group, spleen heat syndrome+Coptidis Rhizoma group, spleen heat syndrome + low-dose eucalyptol group, and spleen heat syndrome + high-dose eucalyptol group. Spleen cold and spleen heat syndromes were induced by disorders of hunger and satiety combined with bitter cold drugs, as well as a high-fat diet combined with liquor. Except for the blank and model groups, the other groups were administered once a day during the modeling process for 14 consecutive days. The general condition and body weight of rats in each group were observed, and the histopathological morphology of the gastric antrum and small intestine was observed by hematoxylin-eosin(HE) staining. The contents of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), Na~+-K~+-ATPase, total cholesterol(TC), triglyceride(TG), gastrin(GAS), motilin(MTL), D-xylose, and other related indices were detected in rats. The expression levels of TRPV1, TRPM8, and UCP1 in small intestine tissue of rats with spleen cold syndrome were detected. The results showed that eucalyptol had a certain degree of improvement in the overall state and body weight of rats with spleen cold syndrome. Compared with the spleen cold syndrome model group, high-dose eucalyptol significantly increased the levels of serum cAMP, cAMP/cGMP, TG, and TC in rats with spleen cold syndrome(P<0.05, P<0.01), decreased the content of cGMP, and significantly elevated the levels of gastrointestinal function-related indicators GAS, MTL, and D-xylose(P<0.05, P<0.01). Low-dose eucalyptol significantly increased the level of cAMP/cGMP in the serum and Na~+-K~+-ATPase levels in hepatic tissue(P<0.05, P<0.01), and significantly increased the levels of GAS and D-xylose(P<0.01). Eucalyptol showed similar effects to Atractylodis Rhizoma with a warm nature on rats with spleen cold syndrome. Compared with the spleen heat syndrome model group, the high-dose and low-dose eucalyptol groups showed a trend of increase in gastrointestinal indicators, with no significant changes in other indicators. In addition, high-dose eucalyptol increased the expression of TRPV1 and UCP1 and decreased the expression of TRPM8 in the small intestine tissue of rats with spleen cold syndrome. Eucalyptol could affect the cyclic nucleotide and material energy metabolism levels of rats with spleen cold syndrome and had a certain improvement effect on their gastrointestinal digestion and absorption function, thereby improving spleen cold syndrome. Eucalyptol had no significant improvement effect on rats with spleen heat syndrome, suggesting that eucalyptol may have a warm nature and regulate spleen meridians. It is speculated that eucalyptol may exhibit its medicinal properties by activating the TRPV1 pathway, promoting the expression of UCP1, and inhibiting the TRPM8 channel.
Animals ; Rats ; Spleen/metabolism* ; Male ; TRPV Cation Channels/genetics* ; Rats, Sprague-Dawley ; Eucalyptol/administration & dosage* ; TRPM Cation Channels/genetics* ; Uncoupling Protein 1/genetics* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Cold Temperature ; Cyclic GMP/metabolism*

This paper aims to study the effect of p-cymene on mice with deficiency-cold syndrome induced by hydrocortisone and deficiency-heat syndrome induced by dexamethasone and explore the medicinal properties and mechanism of p-cymene with mild and warm nature based on the dominant characteristics of the two-way applicable conditions of mild drugs. A total of 80 KM mice were randomly divided into blank group, deficiency-cold syndrome model group, deficiency-cold syndrome + ginseng group, and deficiency-cold syndrome + low-dose and high-dose p-cymene groups, as well as blank group, deficiency-heat syndrome model group, deficiency-heat syndrome + American ginseng group, and deficiency-heat syndrome + low-dose and high-dose p-cymene groups. Hydrocortisone and dexamethasone solution were intragastrically administered for 14 consecutive days to prepare deficiency-cold syndrome and deficiency-heat syndrome models. Except for the blank group and the model group intragastrically administered with normal saline, the other groups were intragastrically administrated with drugs for 14 days. The levels of cyclic adenosine monophosphate(cAMP), cyclic guanosine monophosphate(cGMP), triiodothyronine(T3), thyroxine(T4), total cholesterol(TC), triglyceride(TG), immunoglobin G(IgG), and immunoglobin M(IgM) in serum, as well as the activity of Na~+-K~+-ATPase in liver tissue were detected. The expression of transient receptor potential melastatin 8(TRPM8), transient receptor potential vanilloid 1(TRPV1), and uncoupling protein 1(UCP1) in brown adipose tissue of deficiency-cold syndrome model after intervention with p-cymene was studied. The results showed that p-cymene could effectively improve the levels of cAMP, cAMP/cGMP, TC, IgM, and IgG in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and reduce the content of cGMP. The effects on T3, T4, and TG were not statistically significant. At the same time, p-cymene could reduce the levels of cAMP, cAMP/cGMP, and T4 in serum and the activity of Na~+-K~+-ATPase in liver tissue of mice with deficiency-cold syndrome and increase the levels of cGMP, IgM, and IgG, and it had no effect on T3, TC, and TG. In addition, p-cymene could up-regulate the expression of TRPV1 and UCP1 in brown fat of mice with deficiency-cold syndrome and down-regulate the expression of TRPM8. In summary, p-cymene could significantly regulate the syndrome indexes of mice with deficiency-cold syndrome, and some indexes of mice with deficiency-heat syndrome could be improved, but the effects on lipid metabolism and energy metabolism indexes were not obvious, indicating that the regulation effect of p-cymene on deficiency-cold syndrome model was more prominent and that the medicinal properties of p-cymene were mild and warm. The regulation of TRPV1/TRPM8/UCP1 channel expression may be the molecular biological mechanism of p-cymene with mild and warm nature affecting the energy metabolism of the body.
Animals ; Cymenes ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Disease Models, Animal ; Humans ; Cyclic AMP/metabolism* ; Monoterpenes/administration & dosage* ; Liver/metabolism* ; Cyclic GMP/metabolism* ; TRPV Cation Channels/genetics* ; Uncoupling Protein 1/genetics*

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Through evidence mapping, this paper systematically summarized the research evidence on the use of traditional Chinese medicine(TCM) in treating renal anemia, displaying the distribution of evidence in this field. A systematic search was conducted across databases, including CNKI, Wanfang, VIP, SinoMed, Springner, PubMed, Engineering Village, and Web of Science, targeting studies published up to June 30, 2024. The research evidence was summarized and displayed through a combination of graphs, tables, and text. A total of 264 interventional studies, 37 observational studies, and 7 systematic reviews were included. The annual publication volumes related to TCM treatment in renal anemia showed an overall upward trend, with most studies involving sample sizes between 60 and 120 participants(224 articles, 74.42%). Intervention measures were categorized into 21 types, with oral TCM decoctions being the most common medicine(171 times, 56.81%). The use of self-made prescriptions was the most common TCM intervention method. The intervention duration was mainly between 8 weeks and 3 months(239 articles, 79.40%). The most frequently reported TCM syndrome was spleen and kidney Qi deficiency. The top 2 outcome indicators were the anemia indicators and renal injury/renal function markers. However, several issues were identified in these studies, such as insufficient attention to the sources, social/geographical information, and temporal continuity of research subjects in observational research. Randomized controlled trials mostly had a high risk of bias, mainly due to issues such as randomization bias, blinding bias, and failure to register research protocols. The methodology quality of systematic reviews was generally low, mainly due to inadequate inclusion of literature, failure to specify funding sources, and lack of pre-registrations. While the report quality of systematic review was acceptable, there were significant gaps in the reporting of protocols, registration, and funds. The results show that these issues affect the quality of research and the reliability of findings on TCM in treating renal anemia, underscoring the need to address them to conduct higher-quality research and provide more reliable medical evidence for TCM in treating renal anemia.
Humans ; Anemia/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/drug therapy*

Based on latent structure model and association rule analysis, this study investigates the prescription patterns used by professor YANG Zhong-qi in treating hypertension with traditional Chinese medicine(TCM) and infers the associated TCM syndromes, providing a reference for clinical syndrome differentiation and treatment. The observation window spanned from January 8, 2013, to June 26, 2024, during which qualified herbal decoction prescriptions meeting efficacy criteria were extracted from the outpatient medical record system of the First Affiliated Hospital of Guangzhou University of Chinese Medicine and compiled into a standardized database. Statistical analysis of high-frequency herbs included frequency counts and herbal property-channel tropism analysis. Latent structure modeling and association rule analysis were performed using R 4.3.2 and Lantern 5.0 software to identify core herbal combinations and infer TCM syndrome patterns. A total of 2 436 TCM prescriptions were included in the study, involving 263 drugs with a cumulative frequency of 29 783. High-frequency herbs comprised Uncariae Ramulus cum Uncis, Poria, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, and Alismatis Rhizoma, predominantly categorized as deficiency-tonifying, heat-clearing, and blood-activating and stasis-resolving herbs. Latent structure analysis identified 18 latent variables, 74 latent classes, 5 comprehensive clustering models, and 15 core herbal combinations, suggesting that the core syndrome clusters include liver Yang hyperactivity pattern, Yin deficiency with Yang hyperactivity pattern, phlegm-stasis intermingling pattern, and liver-kidney insufficiency pattern. Association rule analysis revealed 22 robust association rules. RESULTS:: indicate that hypertension manifests as a deficiency-rooted excess manifestation, significantly associated with functional dysregulation of the liver, lung, spleen-stomach, heart, and kidney. Key pathogenic mechanisms involve liver Yang hyperactivity, phlegm-stasis interaction, and liver-kidney insufficiency. Therapeutic strategies should prioritize liver-calming, spleen-fortifying, and deficiency-tonifying principles, supplemented by dynamic regulation of Qi-blood and Yin-Yang balance according to syndrome evolution, alongside pathogen-eliminating methods such as phlegm-resolving and stasis-dispelling. Synergistic interventions like mind-tranquilizing therapies should be tailored to individual conditions.
Hypertension/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Drug Prescriptions ; Latent Class Analysis

This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

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*