Chemical profiling, toxicity assessment, anti-diarrhoeal, anti-inflammatory and antinociceptive activities of Canarium schweinfurthii Engl. (Burseraceae) bark in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Canarium schweinfurthii is used in ethnomedicine for the treatment of diabetes, pain, malaria, fever and diarrhoea. AIM OF THE STUDY: The chemical phytoconstituents, antidiarrheal, anti-inflammatory and antinociceptive effects and safety profile of the aqueous extract of Canarium schweinfurthii bark (AECSB) were investigated. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to analyse the phytochemical composition. In the acute toxicity test, AECSB were administered up to 2 g/kg by oral gavage. For the subacute toxicity test (28 days), rats in group 1 (control) received no AECSB, while rats in groups 2-4 were administered different doses of AECSB. Charcoal meal transit and castor oil-induced diarrhoea models were used to study the antidiarrheal effect, while egg albumin/carrageenan and acetic acid/tail immersion models were used for the anti-inflammatory and antinociceptive studies, respectively. With the exception of the acute toxicity experiment, AECSB was administered orally at doses of 200, 400 and 800 mg/kg. RESULTS: Bioactive phytoconstituents identified include p-cymene, δ-terpinene, linalool and phytol. No adverse effects or mortality were observed in acute and subacute studies. Treatment with AECSB (28 days) had no significant effect on organ weight, biochemical, hematologic and histopathologic parameters compared to the control groups (p > 0.05). Comparable antidiarrheal and antinociceptive effects were observed in both AECSB- and standard drug-treated groups, while the 400 and 800 mg/kg AECSB-treated groups showed remarkable anti-inflammatory effects compared to the standard drug-treated and control groups (p < 0.05). CONCLUSION: AECSB has antidiarrheal, antinociceptive and anti-inflammatory effects and can be safely used for therapeutic purposes.

Phytochemical profile and determination of cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity of aqueous and ethanolic extracts of Pseudobombax marginatum (A. St.-Hil.) A. Robyns.

Pseudobombax marginatum, popularly known as "embiratanha," is widely used by traditional communities as anti-inflammatory and analgesic agent. This study aimed to determine the phytochemical profile as well as cytotoxicity, acute oral toxicity, genotoxicity, and mutagenicity attributed to exposure to aqueous (AqEx) and ethanolic (EtEx) extracts of embiratanha bark. Phytochemical screening was conducted using thin-layer chromatography (TLC). Cell viability was analyzed using MTT assay with human mammary gland adenocarcinoma (MDA-MB-231) and macrophage (J774A.1) cell lines, exposed to concentrations of 12.5, 25, 50, or 100 µg/ml of either extract. For acute oral toxicity, comet assay and micronucleus (MN) tests, a single dose of 2,000 mg/kg of either extract was administered orally to Wistar rats. TLC analysis identified classes of metabolites in the extracts, including cinnamic acid derivatives, flavonoids, hydrolyzable tannins, condensed tannins, coumarins, and terpenes/steroids. In the cytotoxicity assay, the varying concentrations of extracts derived from embiratanha induced no significant alterations in the viability of MDA-MB-231 cells. The lowest concentration of EtEx significantly increased macrophage J774A.1 viability. However, the higher concentrations of AqEx markedly lowered macrophage J774A.1 viability. Animals exhibited no toxicity in the parameters analyzed in acute oral toxicity, comet assay, and MN tests. Further, EtEx promoted a significant reduction in DNA damage index and DNA damage frequency utilizing the comet assay, while the group treated with AqEx exhibited no marked differences. Thus, data demonstrated that AqEx or EtEx of embiratanha may be considered safe at a dose of 2,000 mg/kg orgally under our experimental conditions tested.

Phlomis crinita Cav. From Algeria: A source of bioactive compounds possessing antioxidant and wound healing activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Phlomis crinita Cav. (Lamiaceae), locally known as "El Khayata" or "Kayat El Adjarah", is traditionally used in Algeria for its wound-healing properties. AIM OF THE STUDY: Investigate, for the first time, the phytochemical profile, safety, antioxidant and wound-healing activities of the flowering tops methanolic extract of P. crinita (PCME) collected from Bouira Province in the North of Algeria. MATERIALS AND METHODS: Preliminary phytochemical assays were carried out on PCME to quantify the main classes of bioactive compounds, such as total phenols, flavonoids, and tannins. An in-depth LC-DAD-ESI-MS analysis was carried out to elucidate the phytochemical profile of this plant species. Antioxidant activity was investigated by several colorimetric and fluorimetric assays (DPPH, TEAC, FRAP, ORAC, ß-carotene bleaching and ferrozine assay). The acute oral toxicity of PCME (2000 mg/kg b.w.) was tested in vivo on Swiss albino mice, whereas the acute dermal toxicity and wound-healing properties of the PCME ointment (1-5% PCMO) were tested in vivo on Wistar albino rats. Biochemical and histological analyses were carried out on biological samples. RESULTS: The phytochemical screening highlighted a high content of phenolic compounds (175.49 ± 0.8 mg of gallic acid equivalents/g of dry extract), mainly flavonoids (82.28 ± 0.44 mg of quercetin equivalents/g of dry extract). Fifty-seven compounds were identified by LC-DAD-ESI-MS analysis, belonging mainly to the class of flavones (32.27%), with luteolin 7-(6″-acetylglucoside) as the most abundant compound and phenolic acids (32.54%), with salvianolic acid C as the most abundant compound. A conspicuous presence of phenylethanoids (15.26%) was also found, of which the major constituent is forsythoside B. PCME showed a strong antioxidant activity with half-inhibitory activity (IC50) ranging from 1.88 to 37.88 µg/mL and a moderate iron chelating activity (IC50 327.44 µg/mL). PCME appears to be safe with Lethal Dose 50 (LD50) ≥ 2000 mg/kg b.w. No mortality or toxicity signs, including any statistically significant changes in body weight gain and relative organs' weight with respect to the control group, were recorded. A significant (p < 0.001) wound contraction was observed in the 5% PCMO-treated group with respect to the untreated and petroleum jelly groups between 8 and 20 days, whereas no statistically significant results were observed at the two lower doses (1 and 2% PCMO). In addition, the 5% PCMO-treated group showed a statistically significant (p < 0.05) wound healing activity with respect to the reference drug-treated group, showing, at the end of the study, the highest wound contraction percentage (88.00 ± 0.16%). CONCLUSION: PCME was safe and showed strong antioxidant and wound-healing properties, suggesting new interesting pharmaceutical applications for P. crinita based on its traditional use.

Celosia cristata L.: A review of its traditional uses, phytochemistry, pharmacology, toxicology, and quality control, along with network pharmacological analysis of its components and targets.

ETHNOPHARMACOLOGICAL RELEVANCE: Celosia cristata L. (C. cristata) is a widely used herb in China and has been used as a medicine for more than 1000 years. The herb has been clinically employed to treat various types of bleeding disorders including metrorrhagia, metrostaxis, and leukorrheal diseases, gastrointestinal infections. AIM OF THE STUDY: This review provides a comprehensive analysis of C. cristata, encompassing its botany, traditional applications, phytochemistry, pharmacology, safety, and quality control. Additionally, it delves into the prevailing challenges and limitations with contemporary research concerning C. cristata, thus furnishing valuable insights for future investigations in this domain. MATERIALS AND METHODS: Research data were gathered from authoritative sources including the Pharmacopoeia of China, the Flora of China, as well as various internet databases such as Web of Science, CAS CiFinder, PubMed, Science Direct, and CNKI, along with numerous ancient classics on Chinese herbal medicine. RESULTS: Clinical applications of C. cristata demonstrate its efficacy in treating dysfunctional uterine bleeding, vaginitis, and pelvic inflammatory disease. Presently, seventy-seven compounds have been isolated, including flavonoids, triterpenoids, steroids, organic acids, phenylpropanoids, and alkaloids, with flavonoids and triterpenoids emerging as the primary bioactive constituents. Pharmacological studies reveal its diverse biological activities, such as haemostatic, antitrichomonal, antibacterial, antiviral, analgesic, immunoregulatory, anti-inflammatory, anticancer, hepatoprotective, and antioxidant effects. Leveraging network pharmacology, researchers have embarked on preliminary inquiries into the interplay among chemical constituents, molecular targets and pathological conditions. CONCLUSIONS: C. cristata shows significant potential for use in hemostasis, anti-inflammatory, and antimicrobial treatments. Modern research has revealed its diverse chemical composition and pharmacological activities, making it highly valuable for further study. At the same time, it is necessary to find the characteristic components of C. cristata and establish better quality control standards to better explore its therapeutic potential.

Research progress in the ethnopharmacology, phytochemistry, pharmacology, toxicology, and quality control of Valeriana jatamansi Jones.

ETHNOPHARMACOLOGIC RELEVANCE: Valeriana jatamansi Jones, belongs to the Valerianaceae family, is widely used in traditional Chinese medicine (TCM) and Ayurveda, traditional Indian medicine (TIM). This traditional herb has been officially listed in the pharmacopoeia of sixteen countries. Its usage was first described in Diannan Bencao, also known as "Zhizhuxiang", is a famous folk medicine herb with a long history of medicinal usage in China, and it was used to treat indigestion, flu, and mental disorders in the Han, Achang, Bai, Blang, Dai, Jingpo, Naxi, and Wa ethnic groups. In recent years, V. jatamansi has attracted worldwide attention as an important medicinal due to its pharmacological activity especially in nervous and digestive systems, and multiple uses. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, and quality control of V. jatamansi. MATERIALS AND METHODS: The relevant information of V. jatamansi was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D. and MSc dissertations, using "Valeriana jatamansi Jones", "Valeriana jatamansi", and "" as keywords. After eliminating repetitive and low-quality reports, the remaining reports were analyzed and summarized to prepare this review. Plant information was retrieved by www.worldfloraonline.org and www.gbif.org using "Valeriana jatamansi Jones" as keyword. RESULTS: V. jatamansi has been historically utilized as a traditional medicine to treat various diseases, including infectious, inflammatory, neurological, and gastrointestinal disorders. More than 400 compounds have been identified in V. jatamansi including iridoids, volatile oils, lignans, flavonoids, phenolic acids, phenylpropanoids, sesquiterpenes, sesquiterpene hydrocarbons, triterpenes as well as other compounds. The plant extracts and compounds showed various pharmacological activities such as antitumor, cytotoxic, antivirus, etc. In addition, V. jatamansi has found various applications in the agricultural, food, and cosmetics industry. CONCLUSION: A review of literature shows V. jatamansi has pharmacological properties valuable in treating diseases, particularly for antianxiety and gastrointestinal disorders. Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and in vivo, with a lack of pharmacokinetics, clinical trials and underlying mechanisms. Consequently, it becomes important to embark on additional researchs to elucidate the pharmacokinetics, material basis and mechanisms of V. jatamansi, thereby realizing the aspiration of its comprehensive utilization and sustainable development.

The genus Ranunculus L. (Ranunculus) in Asia: a review of its botany, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations.

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.

Veratrum nigrum L.: A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, toxicity, and incompatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Veratrum nigrum L. (V. nigrum) is a well-known herb with a lengthy history of use in Asian and European countries. V. nigrum has been traditionally used to treat epilepsy, hypertension, malignant sores, and stroke, and it possesses emetic and insecticide properties. AIM OF THE REVIEW: This review summarized the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and metabolism, and toxicity of V. nigrum as well as its incompatibility with other herbs. Current challenges in the use of V. nigrum and possible future research directions were also discussed. MATERIALS AND METHODS: Information on V. nigrum was collected from electronic databases such as PubMed, Google Scholar, Web of Science, CNKI, and WanFang DATA; Masterpieces of Traditional Chinese Medicine; local Chinese Materia Medica Standards; and relevant documents. RESULTS: In ethnomedical practice, V. nigrum has been used as an emetic and insecticide. Approximately 137 compounds have been isolated from V. nigrum, including alkaloids, stilbenes, flavonoids, organic acids, and esters. Its crude extracts and compounds have shown various effects, including anticancer, hypotensive, insecticidal, and antimicrobial activities as well as the ability to improve hemorheological abnormalities. Pharmacokinetic studies have indicated that veratramine (VAM) and jervine have high bioavailability and possibly enterohepatic circulation. In addition, the sex-related pharmacokinetic differences in V. nigrum alkaloids warrant further attention. Toxicological studies have indicated that cevanine-type alkaloids and VAM may be the main toxic components of V. nigrum, and purine metabolism disorders may be related to V. nigrum toxicity. Furthermore, the neurotoxicity and embryotoxicity of V. nigrum have also been observed. The quality control of V. nigrum and the mechanism underlying its incompatibility with other herbs also deserve further research and refinement. CONCLUSION: This review summarized the existing information on V. nigrum, laying the foundation for further studies on this herb and its safe use. Among the various compounds present in V. nigrum, steroid alkaloids are the most numerous and have high content; furthermore, they are closely related to the pharmacological effects of V. nigrum, but their toxicity can not also be ignored. Given that toxicity is a critical issue limiting the clinical application of V. nigrum, more toxicological studies on V. nigrum and its active ingredients, especially steroid alkaloids, should be conducted in the future to further explore its toxicity targets and the underlying mechanisms and to provide more evidence and recommendations to enhance the safety of its clinical application.

Dryopteris crassirhizoma Nakai.: A review of its botany, traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: The Dryopteris crassirhizoma Nakai., a commonly used herb, is known as "Guan Zhong" in China, "Oshida" in Japan and "Gwanjung" in Korea. It has long been used for parasitic infestation, hemorrhages and epidemic influenza. AIM OF THE REVIEW: The present paper aims to provide an up-to-date review at the advancements of the investigations on the traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma. Besides, possible trends, therapeutic potentials, and perspectives for future research of this plant are also briefly discussed. MATERIALS AND METHODS: Relevant information on traditional use, phytochemistry, pharmacological activity, toxicology and pharmacokinetics of D. crassirhizoma was collected through published materials and electronic databases, including the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar, and China National Knowledge Infrastructure. 109 papers included in the article and we determined that no major information was missing after many checks. All authors participated in the review process for this article and all research paper are from authoritative published materials and electronic databases. RESULTS: 130 chemical components, among which phloroglucinols are the predominant groups, have been isolated and identified from D. crassirhizoma. D. crassirhizoma with its bioactive compounds is possessed of extensive biological activities, including anti-parasite, anti-microbial, anti-viral, anti-cancer, anti-inflammatory, anti-oxidant, anti-diabetic, bone protective, immunomodulatory, anti-platelet and anti-hyperuricemia activity. Besides, D. crassirhizoma has special toxicology and pharmacokinetics characterization. CONCLUSIONS: D. crassirhizoma is a traditional Chinese medicine having a long history of application. This review mainly summarized the different chemical components extract from D. crassirhizoma and various reported pharmacological effects. Besides, the toxicology and pharmacokinetics of D. crassirhizoma also be analysed in this review. However, the chemical components of D. crassirhizoma are understudied and require further research to expand its medicinal potential, and it is urgent to design a new extraction scheme, so that the active ingredients can be obtained at a lower cost.

The genus Dioscorea L. (Dioscoreaceae), a review of traditional uses, phytochemistry, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Dioscorea, a member of the Dioscoreaceae family, comprises approximately 600 species and is widely distributed across temperate and tropical regions such as Asia, South Africa, and North America. The traditional medicinal uses of Dioscorea have been documented in Asian and African pharmacological systems. In Asia, this genus is traditionally used to treat respiratory illnesses, rheumatism, diabetes, diarrhea, dysentery, and other conditions. In Africa, this genus has been used to treat human immunodeficiency virus and ring worms. However, the traditional medicinal practices in North America rarely mention the use of this genus. AIM OF THE STUDY: The aim of this review is to comprehensively review the genus Dioscorea, focusing on its traditional uses, phytochemical constituents, pharmacological activities, and potential toxicities. The research also aims to highlight the valuable bioactive compounds within Dioscorea and emphasize the need for further investigations into acute and chronic toxicity, activity mechanisms, molecular markers, and other relevant factors to contribute to the discovery of novel pharmaceuticals. MATERIALS AND METHODS: A search for available information on Dioscorea was conducted using scientific databases, including PubMed, ISI-WOS, Scopus, and Google Scholar, as well as recent academic publications from reputable publishers and other literature sources. The search was not limited by language and spanned the literature published between 1950 and 2022. RESULTS: This article provides a comprehensive review of the Dioscorea genus, focusing on its traditional uses, phytochemical constituents, pharmacological activities, and potential toxicities. Extensive research has been conducted on this genus, resulting in the isolation and examination of over 1000 compounds, including steroids, terpenoids, and flavonoids, to determine their biological activities. These activities include anti-tumor, anti-inflammatory, immunomodulatory, neuroprotective, hypoglycemic, and hypolipidemic effects. However, some studies have indicated the potential toxicity of high doses of Dioscorea, highlighting the need for further investigations to assess the safety of this genus. Additionally, this review explores potential avenues for future research and discusses the challenges associated with a comprehensive understanding of the Dioscorea genus. CONCLUSIONS: Based on the existing literature, it can be concluded that Dioscorea is a valuable source of bioactive compounds that have the potential to treat various disorders. Future research should prioritize the investigation of acute and chronic toxicity, activity mechanisms, molecular markers, and other relevant factors. This review provides a comprehensive analysis of the Dioscorea genus, emphasizing its potential to enable a deeper exploration of the biological activity mechanisms of these plants and contribute to the discovery of novel pharmaceuticals.

In silico and in vivo study of anti-inflammatory activity of Morinda longissima (Rubiaceae) extract and phytochemicals for treatment of inflammation-mediated diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-ß-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

Bioactivity, phytochemistry studies and subacute in vivo toxicity of ethanolic leaf extract of white mulberry (Morus alba linn.) in female mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Morus alba L. leaf extracts (MLE) have been reported for treating hyperglycaemia and diabetes. Phytochemical compounds in the leaves demonstrated the ability to enhance insulin sensitivity and ß-cell secretory function, suggesting their potential value in reducing blood glucose and treating diabetes. However, the phytochemical constituents and safety of the herbal medicines need to be verified in each experimental field from different growing areas. Studies on the phytochemistry and toxicity of Morus alba leaves in Southeast Asia, especially in Brunei, have never been investigated. AIM OF THE STUDY: This study aimed to investigate the bioactivity and phytochemistry of Morus alba ethanolic leaf extract from Brunei Darussalam and its subacute toxic effects in the Institute of Cancer Research (ICR) female mice. MATERIALS AND METHODS: The phenolic yield and antioxidant of the extract were analysed. Meanwhile, liquid chromatography-mass spectrometry and high-performance liquid chromatography were utilised to determine the phenolic compound of the MLE. In the subacute toxicity study, twenty-five female mice were randomly divided into five groups: the control group, which received oral gavage of 5% dimethyl sulfoxide solvent (DMSO), and the MLE treatment group, which received the extract at a dose of 125, 250, 500 and 1000 mg/kg. Physiology, haematology, biochemistry, and histology were evaluated during the study. RESULTS: Morus alba leaf depicted total phenolic 10.93 mg gallic acid equivalents (GAE)/g dry weight (DW), flavonoid 256.67 mg quercetin equivalents (QE)/g DW, and antioxidant bioactivity content of 602.03 IC50 µg/mL and 13.21 mg Fe2+/g DW. Twenty compounds in the Morus alba ethanolic leaf extract were identified, with chlorogenic acid (305.60 mg/100 g DW) as the primary compound. As for subacute toxicity in this study, neither mortality nor haematological changes were observed. On the other hand, administration of 500 and 1000 mg/kg MLE resulted in mild hepatocellular injury, as indicated by a significant (p < 0.05) increase in liver enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The histopathological score showed mild hepatocellular necrosis in administering 250, 500, and 1000 mg/kg of MLE. The parameters of renal injury were within normal limits, with the increase in eosinophilic cytoplasm observed in the histological scoring at 1000 mg/kg of MLE. CONCLUSIONS: Morus alba leaf extract showed abundant polyphenols. In a study on subacute toxicity, MLE caused mild hepatotoxicity in mice. The toxic effect of the extract may be due to kaempferol and chlorogenic acid compounds. The 125 mg/kg MLE dose was safe with no adverse effects.

An ethnopharmacological, phytochemical, and pharmacological overview of onion (Allium cepa L.).

ETHNOPHARMACOLOGICAL RELEVANCE: Onion (Allium cepa L.) is one of the most widely distributed species within the Allium genus of family Amaryllidaceae. Onion has been esteemed for its medicinal properties since antiquity. It has been consumed for centuries in various indigenous cultures for the management of several ailments including microbial infections, respiratory, gastrointestinal, skin and cardio-vascular disorders, diabetes, renal colic, rheumatism, sexual impotence, menstrual pain, and headache. However, so far, there is a scarcity of recent data that compiles the plant chemistry, traditional practices, biological features, and toxicity. AIM OF THE WORK: The aim of this review is to provide a comprehensive and analytical overview of ethnopharmacological uses, phytochemistry, pharmacology, industrial applications, quality control, and toxicology of onion, to offer new perspectives and broad scopes for future studies. MATERIALS AND METHODS: The information gathered in this review was obtained from various sources including books, scientific databases such as Science Direct, Wiley, PubMed, Google Scholar, and other domestic and foreign literature. RESULTS: Onion has a long history of use as a traditional medicine for management of various conditions including infectious, inflammatory, respiratory, cardiovascular diseases, diabetes, and erectile dysfunction. More than 400 compounds have been identified in onion including flavonoids, phenolic acids, amino acids, peptides, saponins and fatty acids. The plant extracts and compounds showed various pharmacological activities such as antimicrobial, antidiabetic, anti-inflammatory, anti-hyperlipidemic, anticancer, aphrodisiac, cardioprotective, and neuroprotective activities. In addition to its predominant medicinal uses, onion has found various applications in the functional food industry. CONCLUSION: Extensive literature analysis reveals that onion extracts and bioactive constituents possess diverse pharmacological activities that can be beneficial for treating various diseases. However, the current research primarily revolves around the documentation of ethnic pharmacology and predominantly consists of in vitro studies, with relatively limited in vivo and clinical studies. Consequently, it is imperative for future investigations to prioritize and expand the scope of in vivo and clinical research. Additionally, it is strongly recommended to direct further research efforts towards toxicity studies and quality control of the plant. These studies will help bridge the current knowledge gaps and establish a solid basis for exploring the plant's potential uses in a clinical setting.

Dysphania ambrosioides (L.) Mosyakin and Clemants: bridging traditional knowledge, photochemistry, preclinical investigations, and toxicological validation for health benefits.

Dysphania ambrosioides L. (Chenopodiaceae) is a Moroccan medicinal plant known locally as "M'Khinza." It is widely used in traditional medicine to treat numerous ailments, such as diabetes, digestive disorders, fever, fertility problems, immune disorders, hypertension, bronchitis, respiratory conditions, pharyngitis, cough, and flu. As part of this review, comprehensive preclinical investigations, including in vitro, in vivo, and in silico studies, were conducted to better understand the mechanisms of action of D. ambrosioides. Additionally, the phytochemical profile of the plant was examined, highlighting the presence of certain bioactive secondary metabolites. The information was gathered from electronic data sources such as Web of Science, PubMed, Science Direct, Scopus, Springer Link, and Google Scholars. Numerous studies have mentioned the pharmacological properties of D. ambrosioides, including its antioxidant, anti-inflammatory, antiparasitic, antiviral, antibacterial, and antifungal activities. Furthermore, research has also suggested its potential as an anticancer, antidiabetic, and vasorelaxant agent. Phytochemical characterization of D. ambrosioides has revealed the presence of over 96 major bioactive compounds, including terpenoids, polyphenols, flavonoids, alkaloids, and fatty acids. As for the toxicity of this plant, it is dose-dependent. Furthermore, more in-depth pharmacological studies are needed to establish the mechanisms of action of this plant more accurately before considering clinical trials. In conclusion, this review highlights the traditional use of D. ambrosioides in Moroccan medicine and emphasizes its potential pharmacological properties. However, to fully harness its therapeutic potential, further research, both in terms of chemistry and pharmacology, is necessary. These future studies could help identify new active compounds and provide a better understanding of the mechanisms of action of this plant, thus opening new prospects for its pharmaceutical application.

Cytotoxicity evaluation of phytochemicals from stingless bee (Tetragonula biroi) propolis.

Three prenylated flavonoids (1-3) were isolated from Tetragonula biroi propolis. The structures of the isolated compounds were characterized by NMR, IR, and UV spectroscopic and mass spectrometric analyses. The cytotoxicity activity of the crude extracts, fractions and the isolated compounds were established against four cell lines such as Caco-2, HeLa, MCF-7, and OVK-18. Among the tested compounds, compound 1 showed cytotoxicity activity against MCF-7 cell lines, whereas compound 2 showed good activity against Caco-2 and OVK-18 cell lines with IC50 values of 14.73 and 14.44, respectively. Moreover, compound 3 exhibited strong activity against OVK-18 cell lines. These findings contribute to the phytochemical understanding of the T. biroi propolis, and their cytotoxicity effects for future pharmaceutical purposes.

Evaluation of phytochemical, antibacterial, thrombolytic, anti-inflammatory, and cytotoxicity profile of Achyranthes aspera aerial part extracts.

This investigation was designed and performed to compare the phytochemical profiling, activities of antibacterial, thrombolytic, anti-inflammatory, and cytotoxicity of methanol extract (ME-E) and aqueous extract (AQ-E) of aerial parts of Achyranthes aspera through in-vitro approach. Also characterize the functional groups of bioactive compounds in the ME-E through Fourier-transform infrared (FTIR) spectroscopy analysis. Interestingly, qualitative phytochemical screening proved that the ME-E contain more number of vital phytochemicals such as phenolics. saponins, tannins, alkaloids, flavonoids, cardiac glycosides, steroids, and phlobatannins than AQ-E. Similarly, the ME-E showed notable antibacterial activity as dose dependent manner against Bacillus subtilis, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa at 1000 µg mL-1 concentration. ME-E also showed 75.2 ± 2% of clot lysis (thrombolytic activity) at 1000 µg mL-1 dosage and it followed by AQ-E 51.24 ± 3%. The ME-E showed moderate and AQ-E demonstrate poor anti-inflammatory activity evidenced by albumin denaturation inhibition and anti-lipoxygenase assays. Furthermore, the ME-E demonstrated a dose dependent cytotoxicity was noted against brine shrimp larvae. In support of this ME-E considerable activities, the Fourier transform infrared (FTIR) analysis confirmed that this extract contain more number peaks attributed to the stretch of various essential functional groups belongs to different bioactive compounds. Hence this ME-E of A. aspera can be considered for further in depth scientific investigations to validate their maximum biomedical potential.

Phytochemical profiling, toxicity studies, wound healing, analgesic and anti-inflammatory activities of Musa paradisiaca L. Musaceae (Plantain) stem extract in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The stem of Musa paradisiaca (plantain) has found application in traditional medicine for the treatment of diabetes, inflammation, ulcers and wound injuries. AIM OF THE STUDY: This study investigated the phytochemical composition, toxicity profile, wound healing, anti-inflammatory and analgesic effects of aqueous Musa paradisiaca stem extract (AMPSE) in rats. METHODS: Phytochemical analysis of methanol-MPSE was performed by gas chromatography-mass spectrometry (GC-MS). Acute toxicity testing was carried out through oral administration of a single dose of AMPSE up to 5 g/kg. Four separate groups of rats were used for the subacute toxicity testing (n = 6). Group 1 served as a normal control and did not receive AMPSE, groups 2-4 received AMPSE daily by gavage for 28 days. In the experiments with excision and incision wounds, the rats were treated with 10 w/w AMPS extract. The anti-inflammatory and analgesic effects of AMPSE were assessed using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute, anti-inflammatory and analgesic studies, AMPSE was administered to the experimental rats at doses of 300, 600 and 900 mg/kg body weight. RESULTS: Bioactive compounds identified include ß-sitisterol, n-hexadecanoic acid, octadecanoic acid, diethyl sulfate, p-hydroxynorephedrine, phenylephrine, nor-pseudoephedrine, metaraminol, pseudoephedrine and vanillic acid. No signs of toxicity and no deaths were observed in all the groups. For the groups treated with AMPSE for 28 days, a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, sodium, chloride, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were observed while high density lipoprotein cholesterol, glutathione and superoxide dismutase increased compared to control (p < 0.05). In wound healing experiments, AMPSE showed greater percent wound contraction and wound resistance fracture compared to the povidone-iodine (PI) treated and control groups. Treatment with 900 mg/kg AMPSE resulted in significant (p < 0.05) anti-inflammatory and analgesic effects compared to the control. CONCLUSION: This study shows that AMPSE is not toxic but contains biologically active compounds with hepatoprotective, anti-inflammatory, lipid-lowering and wound-healing effects. Treatment of rats with AMPSE has shown that AMPSE has anti-inflammatory, analgesic, hepatoprotective, lipid-lowering and wound-healing effects, supporting its therapeutic use in ethnomedicine.

Parkia from Cerrado: phytochemical bioprospection, toxicity and in vitro bioactivities of bark and flower extracts.

Parkia platycephala is the only species of the genus Parkia that is endemic to the brazilian Cerrado and the tree symbol of the state of Tocantins, but there are still few studies regarding its bioprospecting. In this study, we aimed to investigate the phytochemical composition, toxicity and bioactivities of the bark and flower of Parkia platycephala. Hot sequential extractions (Soxhlet) were performed using methanol and hydroethanolic solution (70%), after degreasing the sample (hexane). The presence of flavonoids, tannins, steroids and alkaloids was detected in the preliminary screening. Trilinolein, (Z)-9-octadecenamide, 3-O-methyl-d-glucose were detected by Gas Chromatography coupled to Mass Spectrometry (GC-MS). In the Liquid Chromatography with Diode Array Detector (LC-PDA) analysis, it was detected exclusively ferulic acid (bark) and ellagic acid (flower). The ethanolic extract of the bark (IC50=10.69 ± 0.35 µgmL-1) has an antioxidant potential (DPPH• radical) higher than that of the rutin standard (IC50=15.85 ± 0.08 µgmL-1). All extracts showed excellent anticholinesterase potential (Ellman), with emphasis on the ethanol extract of the flower (IC50 =5.34 ± 0.12 µgmL-1). Regarding toxicity (Artemia salina), the methanolic extract of the bark and the ethanolic extract of the flower presented high and moderate levels, respectively. Such results limit the concentrations of biological activities in this study, however, the antioxidant and anticholinesterase indices fall short of toxicity. The results demonstrated promising antioxidant and anticholinesterase activities of both the bark and the flower of Parkia platycephala.

Nontoxic effects of thymol, carvacrol, cinnamaldehyde, and garlic oil on dung beetles: A potential alternative to ecotoxic anthelmintics.

The sustainability of the traditional extensive livestock sector will only be possible if healthy dung-decomposing insect communities are preserved. However, many current pharmaceutical anthelmintics are harmful to dung beetles, their presence can have a negative impact on biological systems. Phytochemical anthelmintics are an alternative to ecotoxic synthetic pharmaceutical anthelmintics, although ecotoxicological tests of their possible indirect effects on dung beetles are required to demonstrate their viability. In this study, the potential ecotoxicity of thymol, carvacrol, cinnamaldehyde and garlic oil (diallyl disulfide and diallyl trisulfide) were tested for the first time. Inhibition of antennal response was measured as a relevant parameter by obtaining relevant toxicity thresholds derived from concentration‒response curves, such as the IC50. All phytochemical compounds tested were demonstrated to be suitable alternative candidates to the highly ecotoxic compound ivermectin, considering their non-toxicity to nontarget organisms. Residues of the phytochemical antiparasitics found in cattle droppings were extremely low, even undetectable in the case of diallyl disulfide and diallyl trisulfide. Furthermore, our results showed that none of the phytochemical compounds have ecotoxic effects, even at extremely high concentrations, including those almost 1000 times higher than what is most likely to be found in dung susceptible to ingestion by dung beetles in the field. We can conclude that the four selected phytochemical compounds meet the requirements to be considered reliable alternatives to ecotoxic veterinary medicinal products, such as ivermectin.

Phytochemical analysis, antioxidant, α-glucosidase inhibitory activity, and toxicity evaluation of Orthosiphon stamineus leaf extract.

Ocimum aristatum, commonly known as O. stamineus, has been widely studied for its potential as an herbal medicine candidate. This research aims to compare the efficacy of water and 100% ethanolic extracts of O. stamineus as α-glucosidase inhibitors and antioxidants, as well as toxicity against zebrafish embryos. Based on the study findings, water extract of O. stamineus leaves exhibited superior inhibition activity against α-glucosidase, ABTS, and DPPH, with IC50 values of approximately 43.623 ± 0.039 µg/mL, 27.556 ± 0.125 µg/mL, and 95.047 ± 1.587 µg/mL, respectively. The major active compounds identified in the extract include fatty acid groups and their derivates such as linoleic acid, α-eleostearic acid, stearic acid, oleanolic acid, and corchorifatty acid F. Phenolic groups such as caffeic acid, rosmarinic acid, 3,4-Dihydroxybenzaldehyde, norfenefrine, caftaric acid, and 2-hydroxyphenylalanine and flavonoids and their derivates including 5,7-Dihydroxychromone, 5,7-Dihydroxy-2,6-dimethyl-4H-chromen-4-one, eupatorin, and others were also identified in the extract. Carboxylic acid groups and triterpenoids such as azelaic acid and asiatic acid were also present. This study found that the water extract of O. stamineus is non-toxic to zebrafish embryos and does not affect the development of zebrafish larvae at concentrations lower than 500 µg/mL. These findings highlight the potential of the water extract of O. stamineus as a valuable herbal medicine candidate, particularly for its potent α-glucosidase inhibition and antioxidant properties, and affirm its safety in zebrafish embryos at tested concentrations.