Traditional and Integrative Medicine https://jtim.tums.ac.ir/index.php/jtim <p><strong>Traditional and Integrative Medicine&nbsp;</strong>is an international quarterly&nbsp;open access peer-reviewed journal of School of Traditional Medicine published on behalf of Tehran University of Medical Sciences. This journal covering all scientific aspects of traditional, complementary and integrative medicines including history, chemistry, pharmacology, molecular mechanism, proteomics, genomics, metabolomics, safety, quality control, and clinical trial.&nbsp;Traditional and Integrative Medicine provides a bridge connected the tradition medicine system to the modern life science with the efforts of top scientists, as well as a resource to pursuit the solutions for the existing common issues in the traditional medicine. All type of studies including original researches, reviews, systematic reviews, meta-analyses, short communications, case reports, letters and editorials from the scientists in all over the worlds are welcome to this journal.</p> en-US <p>The&nbsp;<em>Traditional and Integrative Medicine</em>&nbsp;allow the author(s) to hold the copyright without restrictions. Also the journal allow the author(s) to retain publishing rights without restrictions.</p> jtim@tums.ac.ir (Dr. Roja Rahimi) journals@tums.ac.ir (TUMS Journals Office) Tue, 30 Jun 2026 21:06:15 +0430 OJS 3.1.1.1 http://blogs.law.harvard.edu/tech/rss 60 Investigating Serum Metabolite Profiles in Healthy Individuals with Hot-Wet and Cold-Dry Temperaments: A Comparative Study Using LC-MS Technique in the Context of Persian Medicine Theory https://jtim.tums.ac.ir/index.php/jtim/article/view/2128 <p>Persian Medicine (PM) categorizes individuals into distinct temperaments (Mizaj) based on their unique morphological, physiological, and psychological characteristics. However, the scientific community requires further evidence to validate these temperament classifications. This study aimed to compare the serum metabolite profiles of healthy individuals with hot-wet and cold-dry temperaments using liquid chromatography-mass spectrometry (LC-MS). A descriptive cross-sectional untargeted metabolomics investigation was conducted between 2022-2023, focusing on 20-25-year-old male participants exhibiting hot-wet and cold-dry temperaments. Blood samples were collected, and their serum metabolite profiles were analyzed using LC-MS. The obtained data were then compared between the two groups, using HMDB, METLIN, KEGG databases, and MetaboAnalyst web-based platform for pathway analysis. Among the 59 differentially expressed metabolites, 56 (94.9%) exhibited significantly higher abundance in individuals with hot-wet temperament compared to those with cold-dry temperament (fold-change ≥1.5, p &lt; 0.05, FDR-corrected q &lt; 0.05, VIP &gt;1.0). Enrichment analysis based on KEGG revealed seven metabolic pathways with higher expression in the hot-wet temperament group compared to the cold-dry group, including the alanine, aspartate, and glutamate metabolic pathways, purine metabolism, arginine and proline metabolism, aminoacyl tRNA biosynthesis, citrate cycle (TCA cycle), the pentose phosphate pathway, and glycolysis and gluconeogenesis. This preliminary study highlights significant differences in the serum metabolic profiles of individuals with hot-wet temperament compared to those with cold-dry temperament, particularly in protein and energy metabolism pathways. These findings provide preliminary biochemical insights into the concept of temperament classification within PM. Further research involving larger and more diverse populations is needed to confirm and expand upon these observations.</p> Afsaneh Arefi Oskouie, Hossein Soraki Aliabad, Rasool Choopani Zanjani, Sajjad Sadeghi, Reyhaneh Farrokhi Yekta, Shahpar Kaveh, Mohammad Fayaz, Zeinab Karimi, Alireza Rahmani ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2128 Sun, 28 Jun 2026 22:54:18 +0430 Complementary and Integrative Medicine Use among Migraine Patients Using a Modified Version of I-CAM-QP: A Cross-Sectional Study https://jtim.tums.ac.ir/index.php/jtim/article/view/2210 <p>This study aimed to determine the prevalence and associated factors of complementary and alternative medicine (CAM) use among patients with migraine using a culturally-adapted Persian version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-QP). In this cross-sectional study, 310 patients attending two neurology referral clinics were screened. After excluding 66 individuals who did not meet International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria and three incomplete questionnaires, 241 patients with ICHD-3–confirmed migraine were analyzed. The core four domains of the I-CAM-QP were preserved (CAM providers, practitioner-based therapies, herbal/supplement use, and self-help practices). Modifications were limited to contextual adaptation and included the addition of migraine-specific clinical variables, incorporation of locally prevalent Traditional Persian Medicine modalities (e.g., cupping, phlebotomy, leech therapy, lifestyle modification), reinstatement and expansion of provider categories to distinguish physician and non-physician practitioners, and supplementary items assessing disclosure and safety-related aspects of CAM use. Participants were predominantly female (78.4%), with a mean age of 38.10 ± 10.18 years and mean disease duration of 10.77 ± 8.7 years. Overall, 91.7% reported using at least one CAM modality in the preceding 12 months. Herbal medicines and dietary supplements were most common (86.7%), with herbs alone reported by 68%. Increasing age was independently associated with higher odds of total CAM use among patients with episodic migraine (AOR 1.08; 95% CI 1.00–1.16) and self-help CAM practices (AOR per year increase: 1.03; 95% CI: 1.00–1.06). Greater mean headache pain intensity was independently associated with visiting a CAM provider (AOR 1.22; 95% CI 1.02–1.47). Additionally episodic migraine was associated with self-help practices (AOR: 2.45; 95% CI: 1.22–4.09). CAM use was highly prevalent and largely self-directed, underscoring the need for structured patient–physician communication in routine migraine care.</p> Farinaz Farhoudi, Alireza Salehi, Maryam Poursadeghfard, Mohammadali Moghimizadeh, Rasool Hasanabadi, Marjan Sarami, Farhad Emadi ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2210 Tue, 30 Jun 2026 18:50:26 +0430 Validity and Reliability of a Questionnaire Based on Unani and Persian Concepts to Assess Sū’-i-Mizāj in Patients with Hypothyroidism https://jtim.tums.ac.ir/index.php/jtim/article/view/2240 <p>Hypothyroidism is not clearly defined in Unani and Persian medical literature, and there is a significant lack of standardized tools to assess Sū’-i-Mizāj (abnormal temperament). The objective of this study was to develop and validate a reliable questionnaire grounded in Unani and Persian texts, aimed at identifying <em>Sū’-i-Mizāj </em>in patients with hypothyroidism.&nbsp;This cross-sectional validation study was conducted at Ajmal Khan Tibbiya College and Hospital, Aligarh (2024–2025). Item generation was performed through an extensive review of classical Unani and Persian texts and expert consultation. Content validity was evaluated using the Content Validity Index (CVI). Reliability was assessed through internal consistency (Cronbach's alpha) and test–retest reliability using the Intraclass Correlation Coefficient (ICC) over a two-week interval. Fifty (50) clinically and biochemically diagnosed hypothyroid patients were recruited, of whom 29 completed both test and retest assessments. Ethical approval was obtained from the Institutional Ethics Committee (Approval No. 1401/FUM), and the study was registered with the Clinical Trial Registry of India (CTRI/2024/02/062913). From an initial pool of 61 items, 48 items were retained across six domains after content validation. The overall Scale Content Validity Index (S-CVI/Ave) was 0.89, indicating strong expert agreement. The questionnaire demonstrated high internal consistency (Cronbach's alpha = 0.89) and excellent test–retest reliability (ICC = 0.97; 95% CI: 0.93–0.98). The 48-item <em>Sū’-i-Mizāj</em> questionnaire demonstrates satisfactory content validity and strong reliability in patients with hypothyroidism. However, given the limited sample size and absence of construct and criterion validity analyses, the findings should be considered preliminary. Further large-scale studies are required to confirm the dimensional structure and establish broader clinical applicability.</p> S M Ahmer, Hina Kafeel ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2240 Tue, 30 Jun 2026 19:09:22 +0430 Kaempferol-Silver Nanoparticle Quercetin Gel for Psoriasis: An In Vitro and In Vivo Preclinical Study https://jtim.tums.ac.ir/index.php/jtim/article/view/2446 <p>This study focuses on developing a novel topical silver nanoparticle (AgNPs) based gel for psoriasis, a chronic inflammatory skin disease affecting over 60 million people worldwide. Conventional therapies are limited by side effects and poor efficacy, highlighting the need for safer and more effective alternatives. Kaempferol (KMP), a natural flavonoid with anti-psoriatic activity, has poor solubility and low bioavailability. To overcome these limitations, kaempferol-silver nanoparticles (KSNPs) were synthesized and incorporated into a quercetin (QRT) gel. The efficacy of the KSNP-loaded QRT gel was assessed through <em>in vitro</em> studies in human keratinocytes, skin irritation testing, and <em>in vivo</em> evaluation in an imiquimod (IMQ)-induced psoriasis model. The formulation aims to enhance skin penetration, stability, and therapeutic outcomes, providing a promising strategy for improved psoriasis management. The formulation exhibited 89.54 ± 1.27% entrapment efficiency with 85.15% cumulative drug release over 24 hours. <em>In vitro</em> assays (HRBC membrane stabilization and protein denaturation inhibition) confirmed strong anti-inflammatory activity, while skin irritancy studies indicated reduced toxicity through KMP-mediated bio-reduction of silver nanoparticles. In the IMQ-induced psoriasis model, topical application of the gel marked a visible reduction in PASI scores, further supported by histopathological evidence. Overall, the KSNP-loaded QRT gel, combining the complementary effects of KMP and QRT, demonstrated controlled drug release and promising therapeutic efficacy for psoriasis and related inflammatory skin disorders. The KSNP-loaded QRT gel shows a promising, safe, and effective topical therapy for psoriasis, leveraging the anti-inflammatory effects of KMP and QRT with enhanced bioavailability through nanoparticle formulation.</p> Siddhi Fogueri, Mrityunjaya Patil ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2446 Tue, 30 Jun 2026 19:17:55 +0430 Study on the Liver-Protecting Properties of Ajuga chamaecistus ssp. tomentella against Acetaminophen-Induced Liver Damage in Rats https://jtim.tums.ac.ir/index.php/jtim/article/view/2468 <p><em>Ajuga</em> species have traditionally been used in Persian medicine to treat conditions such as joint pain, gout, and jaundice. <em>Ajuga chamaecistus</em> ssp. <em>tomentella</em>, known locally as “komafitoos,” is one of the five native species in Iran. This study evaluated the antioxidant and hepatoprotective effects of the aerial part extract of <em>A. chamaecistus</em> ssp. <em>tomentella</em> against acetaminophen-induced liver toxicity in rats. Thirty-six rats were divided into six groups, including a control group receiving normal saline and others were administered with acetaminophen (500 mg/kg) for seven days. The treatment groups received hydro-ethanolic extracts of the plant at doses of 200, 400, and 800 mg/kg by gavage; while silymarin (100 mg/kg) was used as a positive control. Biochemical analyses on day eight measured liver function markers (alanine transaminase, aspartate transaminase, alkaline phosphatase , bilirubin, total protein, and albumin) and oxidative stress indicators (glutathione and malondialdehyde). The extract significantly reduced liver enzyme levels and improved lipid profiles by lowering cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein concentrations compared to the acetaminophen-only group. The 200 mg/kg dose showed the strongest protective effects, preventing glutathione depletion and tissue lipid peroxidation, with histological findings confirming minimal hepatic damage comparable to silymarin. These results suggest that <em>A. chamaecistus</em> ssp. <em>tomentella</em> extract at 200 mg/kg exhibits potent hepatoprotective and lipid-lowering properties against acetaminophen-induced liver injury.</p> Nona Sadat Mousavi Ayatollahi, Seyede Nargess Sadati Lamardi, Omid Sabzevari, Niloofar Nazari, Hamid Reza Monsef Esfehani, Mahdi Vazirian ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2468 Tue, 30 Jun 2026 20:03:44 +0430 Effect of Rosa canina L. Hydroalcoholic Extract on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Rats https://jtim.tums.ac.ir/index.php/jtim/article/view/2580 <p>Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition with increasing global incidence. Given the reported anti-inflammatory, antioxidant, and lipid-lowering properties of&nbsp;<em>Rosa canina</em>&nbsp;L. (RC), this study aimed to evaluate its early-intervention effect on the laboratory and histopathological markers of NAFLD in a rat model. Thirty-six rats were divided into six groups (n=6): a control group on a regular diet, and five groups on a high-fat diet (HFD). The HFD groups received either normal saline (N/S), atorvastatin (10 mg/kg), or RC extract at doses of 300, 500, or 700 mg/kg. After 9 weeks, lipid profiles, liver enzymes (AST, ALT), and histopathological examination of liver biopsies were assessed. Total phenolic content of the extract was also determined. Total cholesterol (TC) levels were significantly reduced in the group receiving 500 mg/kg RC compared to the HFD+N/S group. AST levels were lower in the 300 mg/kg and 500 mg/kg RC groups than in the 700 mg/kg RC and atorvastatin groups. Histopathological analysis revealed ballooning scores of 55-60% in the HFD+N/S group, 30-35% in the atorvastatin group, 65-70% in the 300 mg/kg RC group, 30% in the 500 mg/kg RC group, and 45-55% in the 700 mg/kg RC group. Overall, the findings were generally positive, although the effects differed across the tested doses. Notably, the 500 mg/kg/day dose was associated with more favorable histopathological observations. RC demonstrates significant effects on lipid profile and liver enzymes comparable to atorvastatin in preventing NAFLD. These findings suggest that&nbsp;RC is a promising early-intervention agent for the prevention of NAFLD.</p> Fatemeh Afrashteh, Manijeh Motevalian, Asie Shojaii, Shayan Eghdami, Maryam Abolhasani ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2580 Tue, 30 Jun 2026 21:01:32 +0430 Exploring Parallels: Dry Dystemperament in Persian Medicine and Its Similarities with The Concept of Dietary Advanced Glycation End Products https://jtim.tums.ac.ir/index.php/jtim/article/view/2047 <p>Advanced Glycation End Products (AGEs), productions of non-enzymatic reactions between lipids, amino acids, carbohydrates, and DNA molecules glycation, contribute to the enhancement of oxidative stress and age-associated inflammation leading to chronic disease susceptibility. This study aims to provide a hypothetical interpretation of the relationship between Persian Medicine (PM) dietary recommendations and the process of inflammation-related aging through the consumption of AGEs. We comprehensively summarized recent evidence and PM textbooks using related keywords. Consumption of AGE-rich diets is associated with a high level of circulating AGEs, leading to oxidative stress and inflammatory conditions such as metabolic syndrome. Although foods are the primary source of AGEs in the body, cooking methods can play a role in AGE production: high temperature, longer duration of cooking, cooking surfaces, and lower moisture can increase AGE production, especially during cooking animal-derived foods. This concept has some similarities to the PM doctrine that states that many chronic diseases, such as atherosclerosis, cardiovascular disease, diabetes, and cancers develop from dry dystemperament. Foods with dry temperament, such as low-fiber foods undergoing low-moisture high-heat food processing, can lead to dry dystemperament. Hence, PM recommendations may help design better research studies to understand the dietary triggers of chronic inflammation.</p> Mohammad Sadegh Adel-Mehraban, Media Abedian, Mariam Yavari ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2047 Sun, 28 Jun 2026 22:36:47 +0430 Exploring the Potential of Nutraceuticals in Diabetic Retinopathy: Evidence-Based Mechanisms and Clinical Insights https://jtim.tums.ac.ir/index.php/jtim/article/view/1881 <p>Diabetic retinopathy (DR) is a microvascular consequence of diabetes. Even in the early stages of diabetic retinopathy, oxidative stress can cause damage to retinal vascular endothelial cells. However, in individuals with &nbsp;early-stage DR, effective care is required before the disease progresses to the more serious sight-threatening proliferative stage. This study explores the potential of nutraceuticals in the treatment of DR, focusing on their mechanisms of action as supported by evidence, clinical studies, and commercially accessible formulations. A thorough literature review was conducted to identify relevant research papers and reviews on nutraceuticals for the treatment of diabetic retinopathy. Relevant papers were located using scientific databases such as PubMed, Google Scholar, Elsevier, MDPI, ScienceDirect, and Web of Science. The search includes publications published up to November 2024 that used the standard keywords "Diabetic Retinopathy," "Nutraceuticals," "Evidence-Based Management," "Current Treatments," "Prevention," "Experimental Evidence," "Mechanisms of Action," "Marketed Formulations," "Clinical Studies," and "Future Directions." Nutraceuticals, which are natural functional foods with little adverse effects, have been advocated as therapeutic to people with DR. Many studies, both <em>in vitro</em> and <em>in vivo</em>, have established the benefits of a variety of nutraceuticals in DR, including their antioxidative, anti-inflammatory, neuroprotective, and vasoprotective activities. However, just a few clinical trials have been done, with varying results. Nutraceuticals, which combine natural ingredients with pharmaceutical chemicals, offer therapeutic potential in pathological situations such as DR. Although the findings are confined to animal models and have little bioavailability, they might provide a natural alternative to conventional therapies. Nutraceuticals may protect neurones, enhance retinal function, and activate pathways such as NF-κB and HIF-1α signalling. Diabetes-induced oxidative stress has been shown to increase inflammation and neurodegeneration, resulting in VEGF overexpression and vascular damage. Regardless of its preclinical character, research into interventive nutraceutical treatment may provide encouraging results in clinical applications.</p> Pranjal Sachan, Navdeep Kumar ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/1881 Sun, 28 Jun 2026 18:29:09 +0430 Herbal Medicine in Head and Neck Cancer: A Review of Randomized Controlled Trial https://jtim.tums.ac.ir/index.php/jtim/article/view/1951 <p>Head and neck cancer (HNC) is a significant global health issue, ranking as the seventh most common cancer worldwide in 2020. Standard treatments like surgery, radiotherapy, and chemotherapy often lead to adverse effects such as oral mucositis (OM) and gastrointestinal complications, which negatively impact patients' quality of life (QoL). The use of herbal medicine has emerged as a complementary approach to mitigate these side effects. This review aims to explore and assess the overview and outcomes of herbal medicine use in HNC patients through a review of randomized controlled trial (RCTs) studies. Articles were searched until to October 19, 2024, using two databases: PubMed and The Cochrane Library with the keywords and combinations of ‘AND’ and ‘OR’ to search for relevant studies. Out of 1,312 articles identified, 11 studies met the inclusion criteria. These studies were conducted in diverse regions, including Iran, Japan, Taiwan, India, China, Germany, and Brazil, with sample sizes ranging from 20 to 74 participants. Herbal medicine showed potential benefits in managing OM, improving gastrointestinal motility, and alleviating xerostomia. Herbal medicines demonstrate promising efficacy and safety profiles in managing HNC-related complications, such as OM, gastrointestinal issues, and QoL. These findings suggest the potential integration of herbal medicine into HNC management as an innovative and supportive care strategy.</p> Dimas Setyadi Putra, Bachren Azra Saputra, Deksa Aldebaran, Syntiya Inanda Khoidir ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/1951 Sun, 28 Jun 2026 21:41:43 +0430 The Role of Complementary and Integrative Medicine on Assisted Reproductive Technologies Outcomes: A Comprehensive Review of Preclinical and Clinical Evidence https://jtim.tums.ac.ir/index.php/jtim/article/view/1996 <p>Many infertile couples seek complementary and integrative medicines (CIMs) as adjunctive therapies to enhance the effectiveness of assisted reproductive technologies (ART). Repeated unsuccessful in vitro fertilization (IVF) cycles have prompted patients to explore CIM modalities in hopes of improving their chances of successful conception. This review aims to evaluate the impact of various CIM approaches on IVF outcomes and to summarize the potential mechanisms underlying their effects. A systematic search was conducted across four major scientific databases PubMed, Scopus, Web of Science, and Google Scholar resulting in the identification of 141 relevant studies. These included 87 studies on acupuncture, 35 on traditional herbal medicine, 5 on phytochemicals, 3 on yoga, 2 on massage therapy, 1 on Ayurveda, and 8 studies evaluating the combined use of acupuncture and Chinese herbal medicine. Among the CIM interventions analyzed, acupuncture alone and its combination with Chinese herbal medicine demonstrated the most consistent positive effects on IVF outcomes. Herbal medicines were found to exert beneficial effects through multiple physiological pathways, including the regulation of ovulation, stimulation of follicular development, improvement of menstrual flow, modulation of hormonal balance, and enhancement of endometrial thickness. Massage therapy has been associated with improved IVF success rates, potentially due to its capacity to reduce psychological stress, decrease uterine contractions, and promote abdominal blood circulation. Although yoga has shown promise in alleviating stress and anxiety among women undergoing fertility treatments, current evidence remains limited regarding its direct impact on clinical IVF outcomes such as clinical pregnancy rate. Ayurveda, a traditional system of medicine, may offer a holistic approach for managing unexplained infertility; however, further high-quality research is needed to establish its efficacy in this context.&nbsp; Despite the diversity and volume of existing studies, there is growing evidence supporting the safety, affordability, and potential effectiveness of CIM interventions as adjuncts to ART. These modalities may provide valuable, non-invasive options for enhancing fertility and improving treatment outcomes in infertile couples.</p> Zahra Shaaban, Zahra Taghipour, Mojgan Tansaz, Roja Rahimi, Mohammad Hossein Ayati, Arezoo Moini Jazani ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/1996 Sun, 28 Jun 2026 22:22:26 +0430 The Impact of Curcumin on Sperm Parameters in Men: A Systematic Review https://jtim.tums.ac.ir/index.php/jtim/article/view/2152 <p>Male infertility accounts for 50% of infertility cases among couples. Medical treatments may have side effects; while curcumin has been explored as a therapeutic option due to its antioxidant properties and fewer side effects. This study assessed the effect of curcumin on sperm parameters. This systematic review focused on experimental human studies, searching databases such as PubMed, Web of Science, Scopus, Embase, as well as trial registration databases including trialsearch.who.int and clinicalTrials.gov. Additionally, Persian databases like SID and Magiran were searched up to August 2024, without any time or language restrictions, using keywords related to ″male infertility″, ″sperm analysis″, ″sperm freezing″, and ″curcumin″. The quality of the studies was assessed using the valid and reliable tool from the Joanna Briggs Institute (JBI) for semi-experimental studies. This systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Totally, out of 537 identified studies, 11 studies remained that aligned with the objectives of the current research. The results of the systematic review indicated that curcumin, at doses exceeding 200 micromoles, inhibited sperm motility; while lower doses enhanced it. Furthermore, under oxidative stress conditions resulting from freezing, curcumin improved both sperm motility and viability. Curcumin, as a potent antioxidant, can enhance sperm motility, viability, and DNA integrity; while at higher doses, it may act as a contraceptive agent. Its effects are dose- and time-dependent, and it may help reduce oxidative stress and damage associated with sperm freezing. Further clinical studies are recommended to explore the practical application of curcumin in the treatment of infertility.</p> Fatemeh Rashidi, Sepideh Hajian, Mojgan Zarei Salehabadei, Fatemeh Alahverdi, Fatemeh Kermani, Zohre Keshavarz ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2152 Sun, 28 Jun 2026 23:11:33 +0430 Pharmacological Properties and Neuroprotective Mechanisms of Crotalaria verrucosa L.: an Integrative Approach Bridging Traditional Medicine and Molecular Neuroscience https://jtim.tums.ac.ir/index.php/jtim/article/view/2207 <p><em>Crotalaria verrucosa</em> L. (Fabaceae), or blue rattlepod, is a medicinal plant well-disseminated in tropical and subtropical areas and possesses a wide historical record of traditional use in medicine. Recent phytochemical and pharmacological investigations have revealed an intricate profile of bioactive secondary metabolites, including flavonoids, phenolic acids, terpenoids, phytosterols, and sapogenins, which exhibit impressive antioxidant, anti-inflammatory, hepatoprotective, and cytoprotective properties. This review critically synthesizes current knowledge on the botanical characteristics, phytochemical constituents, and pharmacological activity of <em>C. verrucosa</em>, focusing on its potential neuroprotective properties. Key constituents such as gallic acid, caffeic acid, catechin hydrate, vanillic acid, lupeol, and syringic acid act as reactive oxygen species scavengers and inhibitors of lipid peroxidation, thereby countering oxidative stress. Flavonoids, including (-)-epicatechin, vitexin, and isovitexin, are reported to activate the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway; while β-amyrin, β-sitosterol, and lupeol may influence phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling. Compounds such as caffeic acid, syringic acid, lupeol, and stigmasterol demonstrate anti-inflammatory potential through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways modulation; whereas β-amyrin and β-sitosterol have been implicated in amyloid-β inhibition. Additional evidence suggests a role for phytosterols and sapogenins in cholinergic and GABAergic neurotransmission. Although these mechanistic insights are promising for neuroprotective actions, robust empirical validation in disease-specific <em>in vivo</em> and clinical models is still lacking. Therefore, future studies should prioritize bioactivity-guided fractionation, pharmacokinetics, and safety evaluation to advance <em>C. verrucosa</em> from traditional medicine toward modern drug discovery for neurodegenerative disorders.</p> Kushani Perera, Yugani Rathnayake, Thushani Madurangi ##submission.copyrightStatement## https://jtim.tums.ac.ir/index.php/jtim/article/view/2207 Tue, 30 Jun 2026 18:30:03 +0430