Folk Medicine Research Articles

Atractylodes Lancea and Its Constituent, Atractylodin, Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease via AMPK Activation.

Metabolic dysfunction-associated steatotic liver disease (MASLD), which encompasses a spectrum of conditions ranging from simple steatosis to hepatocellular carcinoma, is a growing global health concern associated with insulin resistance. Since there are limited treatment options for MASLD, this study investigated the therapeutic potential of Atractylodes lancea, a traditional herbal remedy for digestive disorders in East Asia, and its principal component, atractylodin, in treating MASLD. Following 8 weeks of high-fat diet (HFD) feeding, mice received oral doses of 30, 60, or 120 mg/kg of Atractylodes lancea. In HFD-fed mice, Atractylodes lancea treatment reduced the body weight; serum triglyceride, total cholesterol, and alanine aminotransferase levels; and hepatic lipid content. Furthermore, Atractylodes lancea significantly ameliorated fasting serum glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance levels in response to HFD. Additionally, a glucose tolerance test demonstrated improved glucose homeostasis. Treatment with 5 or 10 mg/kg atractylodin also resulted in anti-obesity, anti-steatosis, and glucose-lowering effects. Atractylodin treatment resulted in the downregulation of key lipogenic genes (Srebf1, Fasn, Scd2, and Dgat2) and the upregulation of genes regulated by peroxisome proliferator-activated receptor-α. Notably, the molecular docking model suggested a robust binding affinity between atractylodin and AMP-activated protein kinase (AMPK). Atractylodin activated AMPK, which contributed to SREBP1c regulation. In conclusion, our results revealed that Atractylodes lancea and atractylodin activated the AMPK signaling pathway, leading to improvements in HFD-induced obesity, fatty liver, and glucose intolerance. This study suggests that the phytochemical, atractylodin, can be a treatment option for MASLD.

Holothuria polii Extract as a Potential Anticoccidial Agent: Evidence of Its MUC2 Regulatory Impact in Murine Jejunum.

Eimeria is a parasite that causes coccidiosis in a variety of animals, leading to nutritional imbalances, issues with food digestion and absorption, low weight, and intestinal inflammation of varying degrees in its hosts. Anticoccidial medication resistance has become a significant obstacle to disease control efforts, leading to a renewed focus on discovering novel chemicals for alternative therapeutic approaches. The purpose of this study was to determine the efficacy of Holothuria polii extract (HpE) in treating eimeriosis in mice. Five groups of mice were studied, with E. papillata sporulated oocysts (1 × 103) used to infect three groups experimentally. The first group was treated with 200 mg/kg of HpE, the second group with Amprolium (120 mg/kg), and the third group was left untreated as a control. The fourth and fifth groups were uninfected, with one of them treated with 200 mg/kg of HpE and the other used as a negative control. The results revealed that HpE has 10 phytochemical compounds according to GC-MS analysis. Treatment with HpE resulted in a substantial decrease in oocyst output in feces. Also, the parasitic stages showed morphometric alterations, with reductions in the measurements compared with the infected, untreated mice. Moreover, expression of the mucin gene (MUC2) was higher in treated mice compared to infected ones, with significant increases in goblet cell numbers, which provided additional evidence for the activity of HpE as an anticoccidial product. In conclusion, there are a wide variety of natural products and many have been employed in folk medicine for treating a range of parasitic diseases.

Discovery of a potent, Kv7.3-selective potassium channel opener from a Polynesian traditional botanical anticonvulsant

Plants remain an important source of biologically active small molecules with high therapeutic potential. The voltage-gated potassium (Kv) channel formed by Kv7.2/3 (KCNQ2/3) heteromers is a major target for anticonvulsant drug development. Here, we screened 1444 extracts primarily from plants collected in California and the US Virgin Islands, for their ability to activate Kv7.2/3 but not inhibit Kv1.3, to select against tannic acid being the active component. We validated the 7 strongest hits, identified Thespesia populnea (miro, milo, portia tree) as the most promising, then discovered its primary active metabolite to be gentisic acid (GA). GA highly potently activated Kv7.2/3 (EC50, 2.8 nM). GA is, uniquely to our knowledge, 100% selective for Kv7.3 versus other Kv7 homomers; it requires S5 residue Kv7.3-W265 for Kv7.2/3 activation, and it ameliorates pentylenetetrazole-induced seizures in mice. Structure-activity studies revealed that the FDA-approved vasoprotective drug calcium dobesilate, a GA analog, is a previously unrecognized Kv7.2/3 channel opener. Also an active aspirin metabolite, GA provides a molecular rationale for the use of T. populnea as an anticonvulsant in Polynesian indigenous medicine and presents novel pharmacological prospects for potent, isoform-selective, therapeutic Kv7 channel activation.

Treatment of acute pharyngitis in rats with season tea decoctions from traditional Chinese medicine through a synergistic and subtle regulation of ARNTL and BHLHE40

Ethnopharmacological relevanceWhile the seasonal variations in the human immune function and many infectious diseases are well-known, to develop therapeutic strategies regarding such seasonality is quite challenging. However, some traditional medical practices have already taken the seasonality into account, such as the “Season Tea” (ST) decoctions investigated in the present study. Aim of the studyWe present a study of the ST decoctions from traditional Chinese medicine, which include four formulae designed for the four seasons, aiming to investigate their pharmacological commonality and distinction. Materials and methodsA rat model of acute pharyngitis was utilized for the pharmacological study, and the effects of the ST decoctions were evaluated through histology, biomedical assays, microarray analysis, real-time quantitative PCR and Western blot. ResultsThe experimental data show that all of the four ST formulae display good pharmaceutical effects on acute pharyngitis, and circadian rhythm appears to be a significant pathway for investigating their pharmacological commonality and distinction. Specifically, while all of the four ST decoctions can regulate the circadian-rhythm-related genes ARNTL and BHLHE40, the regulation is along different directions with the modification of the supplements and the substrates in each ST formula. ConclusionThese results indicate the correlation between the acute pharyngitis and circadian rhythm, and illustrate the possibility of synergistically and subtly regulating ARNTL and BHLHE40, which is significant for relevant drug development.

Potential Anti-Obesity Effect of Hazel Leaf Extract in Mice and Network Pharmacology of Selected Polyphenols

Background: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. As a by-product of hazelnut, hazel leaf is usually disposed of as waste, but it is widely used in traditional and folk medicines around the world. Aim of this study: Based on previous studies, the effects of the regulation of lipid metabolism and the mechanism of hazel leaf polyphenol extraction obesity were investigated. Methods: In this study, a high-fat diet-fed mouse model of obesity and 3T3-L1 preadipocytes were established. The ameliorative effects of the hazel leaf polyphenol extract on obesity and the regulating lipid metabolisms were explored based on network pharmacology, gut microbiota, and molecular docking. Results: Network pharmacology showed that hazel leaf polyphenols may play a role by targeting key targets, including PPARγ, and regulating the PPAR signaling pathway. They significantly improved body weight gain, the liver index, and adiposity and lipid levels; regulated the gut microbiota and short-chain fatty acid contents; down-regulated the expression of lipid synthesis proteins SREBP1c, PPARγ, and C/EBP-α; and up-regulated the expression of p-AMPK in obese mice. They inhibited the differentiation of 3T3-L1 cells, and the expression of related proteins is consistent with the results in vivo. The molecular docking results indicated that gallic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin, myricetin, and luteolin-7-O-glucoside in the hazel leaf polyphenol extract had strong binding activities with PPARγ, C/EBP-α, and AMPK. Conclusions: The results demonstrate that the hazel leaf polyphenol extract can improve obesity by regulating lipid metabolism, which provides a valuable basis for developing health products made from hazel leaf polyphenols in the future.

Cannabidiol finds dihydrocannabidiol as its twin in anti-inflammatory activities and the mechanism

Ethnopharmacological relevanceThe hemp (cataloged at the “Medicinal Plant Names Services” as Cannabis sativa L.) extracts, cannabinoids have been used for centuries in Southeast Asia as folk medicines and now authorized by about 50 countries for application in medicine, health care products and cosmetics. As the most consumed cannabinoid, cannabidiol (CBD) has been recognized due to its various bioactivities, including anti-inflammatory and antibacterial properties. Aims of the studyThe utilization of CBD is limited due to its potential conversion to psychoactive Δ9-tetrahydrocannabinol in strong acidic environment, demanding to excavate safer alternatives with clarified bioactivities. Yet the anti-inflammatory and antibacterial properties of CBD still remain unknown, in both of the performances and the corresponding mechanisms. Previously, a synthetic CBD analogue, H2CBD (Dihydrocannabidiol) was found to be effective as CBD does towards some antioxidantive activities and mouse seizure mitigation. Therefore, it is wondering if H2CBD also acted similarly as CBD does in the aspect of anti-inflammatory performance and mechanism, and the safety. Material and methodsThe anti-inflammatory properties of CBD and H2CBD were revealed with enzymatic assays, proteins denaturation and lipopolysaccharide (LPS) stimulated RAW264.7 cells model, with epigallocatechin gallate (EGCG) as the positive control. Their anti-inflammatory mechanism was revealed with ELISA and Western blot assay. The antibacterial properties of CBD and H2CBD were also investigated towards E. faecalis and B. cereus along with their synergistic effect with commercial antibiotics. ResultsCBD and H2CBD exhibited almost same (P > 0.05) performance in all the assayed anti-inflammatory properties, yet their anti-inflammatory efficiencies positively correlated to their antioxidantive activity. Moreover, both of CBD and H2CBD presented anti-inflammation to LPS stimulated RAW264.7 cells through NF-κB and AKT pathway. Furthermore, CBD and H2CBD also supplied strong and very similar (P > 0.05) antibacterial activities, comparable to tetracycline in same dose and strength. The erythrocyte hemolytic assay indicates CBD and H2CBD possessing the same safety. All the combinations of H2CBD with other cannabinoids or antibiotics present no antagonism against the bacteria, but nice synergistic or additive effect in some cases. ConclusionCBD and H2CBD presented very similarly in all the assayed anti-inflammatory performances, undergoing same inflammatory mechanism with NF-κB and AKT pathway; they also expressed similar antibacterial activity, like twins. These findings will supply CBD a sustainable, safer and economic alternative with same excellent performances.

Composition, medicinal values, and threats of plants used in indigenous medicine in Jawi District, Ethiopia: implications for conservation and sustainable use

Indigenous knowledge of medicinal plants is vital to local communities and cultural heritage, particularly in Ethiopia. This study aims to document native medicinal plants in the Jawi district, including associated traditional knowledge. The study involved conducting semi-structured interviews, focus group discussions, and guided field walks with a purposefully selected 54 traditional healers. The study identified 87 medicinal plant species from 50 families used treat over 50 ailments, with a preference for wild herbs. Fabaceae, Malvaceae, and Solanaceae were the most prominent families, each with five species; Zehneria scabra, was the most often mentioned species, followed by Lepidium sativum, Myrica salicifolia, Carissa spinarum, and Momordica foetida. 43% of identified species were herbs, with 44% of remedies made from roots. Pounding was the most common preparation method, and oral application was the most frequent use, followed by dermal application. 60% plants treated human ailments, 16% treated livestock, and 24% were used for both. Preference rankings indicated specific plants favored for certain ailments. The study highlights key plant families and species crucial for local healthcare but notes threats like habitat destruction and knowledge loss. Urgent conservation actions are needed to preserve medicinal plants and inform future research and strategies.

Development of Indonesian Original Medicines Study of Standardized Herbal Medicine Products "Antangin JRG" as Traditional Medicine

This study aims to examine the potential for the development of indigenous Indonesian medicines based on traditional medicinal plants. Herbal medicine has been used for generations in Indonesia and has great potential to be developed into more standardized and modern products. This study covers various aspects ranging from product name, content, class, composition, efficacy claims, empirical data, standardization of raw materials, preclinical tests, toxicity tests, to clinical trials. The results of the study show that with proper processing and standardization, Indonesian traditional medicine can compete with modern pharmaceutical products.

Artificial neural network models for forecasting the extracted yield of essential oils from Curcuma longa L. by hydro-distillation

Abstract Turmeric is commonly acknowledged in traditional medical practices for its strong healing properties. In the present work, hydro-distillation was employed to extract essential oils from turmeric powder. The response surface methodology (RSM) was applied to investigate the effects of various parameters, including evaporation rate (0.23, 0.5, 0.8, 0.97, 1.36, 2 ml/min), solid/liquid ratio (4:100, 6:100, 8:100, 1:10, 11:100 g/ml), and extraction duration (13–250 min) on the yield of essential oils. The central composite design (CCD) proved to be an effective tool for evaluating the extraction yield of essential oils. A three-layer artificial neural network (ANN) was utilized to develop the extraction model, employing the Levenberg–Marquardt (LM) optimization algorithm. The neural network’s input layer comprised the solid/liquid ratio, evaporation rate, and extraction time, while the output layer indicated the yield of essential oil extraction. The most appropriate model included a hidden layer with 16 neurons, achieving R 2 and MSE values of 0.9989 and 0.0013, respectively. This investigation indicates that an artificial neural network prediction model serves as an effective method for estimating essential oil yield.

Identification of antibacterial constituents from Rhododendron simsii Planch with an activity-guided method.

Bacterial infections and antibiotic resistance pose significant public health challenges globally. Natural products serve as valuable sources for discovering antimicrobial agents. Rhododendron simsii Planch, a folk medicine, is traditionally used to treat various inflammatory diseases. In this study, we investigated the antibacterial metabolites derived from R. simsii Planch. Rhodosimsiin A (1), bearing a 1,5-seco-1,6 and 3,6-epoxy grayanane diterpene skeleton, representing a novel 5/6/7/6/5 pentacyclic ring system, and 3β,16α-dihydroxy-6β-ethoxy-14β-acetoxy-grayan-1(5)-ene-10-one (4), which represents the first example of the degradation of C-20 and carbonylation in C-10 diterpenoid, together with two new grayanane diterpenes (2-3), three new triterpenes (13-15), and known analogs (5-12, 16-30), were isolated from the leaves of R. simsii Planch by using the bioassay-guided method. Their structures were elucidated by comprehensive spectroscopic analyses, and absolute configurations were established by single-crystal X-ray diffraction and calculated ECD spectra. Compounds 14, 15, 18, 20, 27, 28, and 30 exhibited potent antibacterial activity with an MIC50 of 1.4-24.3μg/mL against Staphylococcus aureus. The findings of this research indicate that secondary metabolites derived from R. simsii Planch are promising natural antimicrobial candidates.

Advancing Cardiovascular Health: Unveiling the Role of Traditional and Natural Medicine

In the quest for optimizing cardiovascular health, contemporary research increasingly explores the potential benefits of traditional and natural medicinal modalities. This paper provides insights into the therapeutic avenues offered by traditional medicine systems and natural remedies in cardiovascular care. Incorporating knowledge from ancient healing traditions like Ayurveda and Traditional Chinese Medicine (TCM) alongside contemporary research on the efficacy of natural compounds, the paper aims to elucidate their cardiovascular effects. Specifically, it examines the impact of lifestyle modifications, dietary supplements, and botanical extracts on cardiovascular health. Synthesizing evidence from clinical trials, preclinical studies, and traditional knowledge systems, the paper underscores the importance of integrating traditional and natural medicine practices with conventional medical interventions. This integration is vital for enhancing our understanding and management of cardiovascular diseases, contributing to more effective preventive strategies and optimized therapeutic outcomes in cardiovascular medicine.

Sanctified Trees (Ficus religiosa and Ficus benghalensis) in India: A Significance and Analogous Mythology

Sanctified trees are the trees of religious importance and cultural significance. In India, trees particularly Ficus benghalensis and Ficus religiosa are such sacred plants with exceptional therapeutic qualities. Because of their aesthetic and natural characteristics, these plants are valued. Thus, in order to preserve certain plants, our ancestors associated certain Gods and Goddesses with them and designated them as sacred plants. Many people still believe in myths and beliefs associated with sacred trees. These historical notions demonstrate the relationship between people and plants, which is also beneficial in the protection of plant species because of their special features. They possess remarkable medicinal qualities that have assisted in the treatment of numerous life-dangers illnesses. These trees were used in the traditional medical practices of Ayurveda, Siddha, Unani, and homeopathy and often used as a medication for several illnesses. Different plant parts were employed to treat numerous fatal illnesses, including diarrhea, menorrhagia, leucorrhea, dysentery, mental diseases, and tonic and astringent. Therefore, the current review is the initiative to do a thorough literature on its phytochemistry, pharmacognosy, conventional and medicinal purposes along with myths and beliefs attached to it.

Prevalence and Home Management Practice Of Febrile Convulsion Among Children Admitted In a Tertiary Institute Of A Developing Country

Introduction/Objectives Febrile convulsion (FC) is a convulsion triggered by fever of extra-cranial origin in young children between the ages of 3 months and 5 years. The objectives of this study were to determine the prevalence and home management practices of children admitted in the children emergency room (CHER), UCTH, Calabar, Nigeria. Methods/Materials A cross-sectional descriptive study, carried out using quantitative and qualitative methods (admission register and key informant interview). Any child with febrile convulsion admitted into CHER from June 2017 to May 2018 was recruited for the study and his/her caregiver was interviewed on the home practices in the management of FC. Quantitative data was analyzed with SPSS version 22.0 while thematic coding was used for the qualitative data. Results Out of 1,093 total admissions for the periodunder review, 37 had FC giving a prevalence of 3.4% with a M:F ratio of 1.1:1. Malaria was the most common cause in 59.5%. Caregivers treated FC at home by giving the children palm oil, palm kernel oil and crude oil to drink, rubbing olive oil, heating child’s feet on fire and using spoon to keep the mouth open, while some rushed the child to the hospital immediately. Conclusion The prevalence of FC was low and most of the home remedies applied by caregivers were harmful. It is recommended that there is need to intensify health education and create more awareness on the proper management of FC among caregivers in Calabar.

Prevalence and factors associated with the use of traditional medicine in individuals with hypercholesterolemia, hyperglycaemia, and arterial hypertension in Ecuador: results from a population-based study in two health districts.

While traditional medicine (TM) is employed by a significant portion of the global population for managing health issues, clinical guidelines and state recommendations often overlook this practice. The aim of this study was to describe the frequency of use of TM to control 3 metabolic risk factors (MRF): hypertension, hypercholesterolemia, and hyperglycaemia; and the sociodemographic, economic, and clinical characteristics associated with the use of TM. Cross-sectional descriptive study that analyses data obtained from a representative population survey in 2 health districts, one urban in the south of Quito and another in a forested rural area with diverse ethnic groups in Esmeraldas, Ecuador. We include 602 individuals with at least one MRF. We calculated the proportion of people reporting the regular use of TM (herbal or traditional remedy) to control their MRF and we assessed potential associations with sociodemographic, economic, and clinical characteristics with a multivariable logistic regression model. In two very different sociocultural contexts in Ecuador we found that use of TM to control MRF was frequent (39.4% in Esmeraldas, 31.1% in Quito), frequently in combination with CM. There is a notable percentage of people, 33.9% in Esmeraldas and 39.0% in Quito, who did not take any treatment for their MRF, and the remainder used CM alone. In both settings, an individual's education lever was significantly associated with TM use. Whereas in Quito individuals with higher education more frequently treated their MRF with TM (aOR 2.04, 95% CI 1.03-3.90), in the rural, hard-to-reach context of Esmeraldas, it was more frequent among people with no formal schooling (aOR: 3.76; 95%CI 1.59-8.88), as well as those of younger age (aOR by year: 0.97; 95% CI 0.95-0.99) and afro ethnicity (aOR: 2.13; 95%CI 1.02-4.45). Traditional medicine is used by a significant proportion of the population in Ecuador, highlighting the need for a more accessible and intercultural healthcare approach. The health system should ensure access to the necessary information and resources for the management of their metabolic risk factors.

Management of Necrotic Transmetatarsal Amputation with <i>Argania</i> Honey Dressing: A Case Report

Chronic wounds represent a significant global health concern, accounting for a considerable proportion of amputations. Recent advances in healthcare have highlighted the importance of effective wound healing and the prevention of bacterial infections, as these factors are crucial contributors to elevated morbidity rates. Selecting an appropriate wound dressing has presented a significant challenge for healthcare professionals, particularly in developing countries. Honey, a traditional remedy with a long history of use, has been employed in wound care for centuries. This report presents a case study of effective management in a 74-year-old patient with a 28-year history of type II diabetes. This individual experienced a complication related to diabetic foot issues, necessitating toe amputation. This procedure subsequently resulted in difficulties involving necrosis. The treatment protocol included the application of a dressing based on pure Argania honey (Argania spinosa, an endemic tree of southwestern Morocco), without additives, pasteurisation or manipulation. A sharp debridement procedure was previously performed to facilitate the impregnation of honey in the affected area of necrosis. At the end of the treatment all symptoms, including pain, exudates, odour, burning sensation and itching, were fully alleviated. Moreover, a considerable decrease in swelling and wound size was evident, suggesting significant healing in the injured area. The administration of natural remedies for the treatment of this kind of injury may prove an efficacious strategy for the enhancement of quality of life for diabetic patients.

Strengthening the traditional medicine regulation, education and practice in Nigeria

Background: Despite tremendous advances in medical sciences still a large section of the population in rural areas is heavily dependent on indigenous and Traditional Medicine (TM) for treatment. Moreover, there has been a resurgence of interest in the use of Complementary and Alternative Medicine (CAM), globally. Objective: To review the overall regulator structure for the control of TM and the course curriculum for TM education in Nigeria. Method: Information on CAM and TM was collected via online search. Results: Responding to this unprecedented situation government of many countries have taken proactive steps to streamline and regulate the practitioners of CAM and TM in their countries as mandated by WHO. In many African countries because of the availability of research and training programs many traditional herbal medicines are now being sold over the counter. However, the situation is different in Nigeria, even though TM is very popular across the country, structured institutionalized teaching and research activity on TM are inadequate. Conclusion: Health is a key component in determining the Human Development Index (HDI) of a country. CAM and TM practitioner may play an important role in improving the HDI score of the country. Government-sponsored education & training program for TM practitioners is crucial.

Metabolomics analysis of (Geo)propolis from Brazilian stingless bees by FIA and UHPLC-HRMS (Orbitrap)

Native stingless bees (Meliponini) from Brazil make (geo)propolis which is largely used in folk medicine, specially by indigenous and quilombos communities and beekeepers´ families but are progressively being recognized for their pharmacological activities. In this study, the ethanolic extracts of (geo)propolis (EEGs) from Melipona marginata, M. quadrifasciata, M. scutellaris, and Tetragonisca angustula were analysed by Flow injection analysis (FIA) and Ultra-high performance liquid chromatography (UHPLC) in a high resolution Orbitrap mass analyser (HRMS) to investigate and compare their chemical profile. Untargeted metabolomic approach based on UHPLC-HRMS experiments, and bioinformatic tools, allowed to annotate 59 compounds from diverse classes such as: flavonoids, phenolic compounds, sugars, terpenoids, and lipids. In addition, using multivariate tools and Flow injection- high resolution mass spectrometry (FIA-HRMS), it was possible to classify samples and identify marker ions related to the bee species or genus and to the geographical origin as a proof of concept.

Comparative evaluation of anticancer potential of Spilanthes paniculata leaf and flower essential oil using annexin V and orosphere formation in oral cancer cell line.

Spilanthes paniculata, a member of the Asteraceae family, is predominantly used as a traditional remedy in addressing oral ailments, particularly gum infections and sore throat. The flowers are chewed to alleviate toothache immediately. This study evaluated a comparison between the essential oils of leaf and flower derived from Spilanthes paniculata targeting the SCC9 oral cell lines using in vitro and in silico approaches. The anticancer activity was performed through an MTT assay, apoptosis assays using annexin V and orospheres formation assays. Molecular docking was performed between five selected phytocompounds against the p53 protein by using AutoDock 4.2.6 software. The results confirmed that the flower essential oil significantly reduced the cell viability in a dose-dependent manner, with an IC50 value of 113.95µg/mL. The apoptosis assays showed that the flower essential oil was approximately 2.5 times more effective in inducing early apoptosis at 50µg/mL compared to the essential oil of the leaf. The orosphere formation assays further confirmed the anticancer potential of the flower essential oil. Spathulenol exhibited strong hydrogen bonding with the p53 protein. The ADMET prediction tools were used to predict the in silico pharmacokinetics and drug-like properties of the phytoconstituents. The results suggested that Spathulenol and Nerolidol have high gastrointestinal absorption (GIA), with estimated solubility (ESOL) values of -3.17 and -3.22, respectively, falling within the optimal range. These findings suggest that the flower's essential oil efficiently prevented the proliferation of oral cancer and observed a notable degree of cell death, inducing apoptosis and suggesting its significant antiproliferative activity against cancerous cell line which could be explored further for therapeutic applications.

Analgesic and Anti-Arthritic Potential of Methanolic Extract and Palmatine Obtained from Annona squamosa Leaves

Background/Objectives: Annona squamosa is used in folk medicine to treat pain and arthritis. Palmatine is an alkaloid isolated from several plants, including A. squamosa leaves. The aim of the present study was to investigate the analgesic, anti-arthritic, and anti-inflammatory potential of the methanolic extract of A. squamosa (EMAS) and palmatine. Methods: The chemical profile of EMAS was evaluated by ultra high-performance liquid chromatography with electrospray ionization coupled to mass spectrometry (UHPLC-ESI/MS). EMAS and palmatine were evaluated in carrageenan-induced pleurisy, zymosan-induced joint inflammation, formalin-induced nociception, and tumor necrosis factor (TNF)-induced mechanical hyperalgesia in experimental models in mice. A cytotoxicity test of EMAS and palmatine was performed using a methylthiazolidiphenyl-tetrazolium (MTT) bromide assay. Results: The analysis of the chemical profile of the extract showed the presence of palmatine, liriodenine, and anonaine. Oral administration of EMAS and palmatine significantly reduced leukocyte migration and oxide nitric production in the carrageenan-induced pleurisy model. EMAS and palmatine reduced mechanical hyperalgesia, leukocyte migration, and edema formation in the joint inflammation induced by zymosan. In the formalin test, palmatine was effective against the second-phase nociceptive response, mechanical hyperalgesia, and cold allodynia. In addition, palmatine reduced mechanical hyperalgesia induced by TNF. EMAS and palmatine did not demonstrate cytotoxicity. Conclusions: The present study showed that A. squamosa and palmatine are analgesic and anti-inflammatory agents, and that the anti-hyperalgesic properties of palmatine may involve the TNF pathway. Palmatine may be one of the compounds responsible for the anti-hyperalgesic and/or anti-arthritic properties of this medicinal plant.

Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms

Ethnopharmacological relevanceTrifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain. Aim of the studyTo investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action. Materials and methodsThe antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting. ResultsTREO exerted significant antinociceptive activity (P < 0.01) in both phases of the formalin-induced test; however, its effects were more pronounced in the second phase. Modulators of the NO-cGMP-K+ channel pathway significantly reversed the antinociceptive activity of TREO (P < 0.05). Additionally, antagonists of TRPV1 and TRPV2, as well as CB1 and GABAA receptors, significantly reversed the antinociceptive effects of TREO (P < 0.05). In another study, both TREO and Qc significantly attenuated hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced nociception model. Notably, TREO also reduced the expression levels of interleukin-1 beta, interleukin-2, and tumor necrosis factor alpha in CCS-induced rats (P < 0.05). ConclusionTREO and Qc exhibit both antinociceptive and anti-neuropathic activities. The antinociceptive effects are partially mediated through the NO-cGMP-K+ channel pathways, along with the activation of TRPV, GABA, and cannabinoid receptors. Furthermore, the anti-neuropathic activity of TREO may be partially regulated through the inhibition of cytokines.