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A review of Acalypha indica L. (Euphorbiaceae) as traditional medicinal plant and its therapeutic potential

Zahidin NS, Saidin S, Zulkifli RM, Muhamad II, Ya'akob H, Nur H

J Ethnopharmacol, 2017 Jul 31;207:146-173.
PMID: 28647509 DOI: 10.1016/j.jep.2017.06.019

ETHNOPHARMACOLOGICAL RELEVANCE: Acalypha indica is an herbal plant that grows in wet, temperate and tropical region, primarily along the earth's equator line. This plant is considered by most people as a weed and can easily be found in these regions. Although this plant is a weed, Acalypha indica has been acknowledged by local people as a useful source of medicine for several therapeutic treatments. They consume parts of the plant for many therapeutics purposes such as anthelmintic, anti-ulcer, bronchitis, asthma, wound healing, anti-bacterial and other applications. As this review was being conducted, most of the reports related to ethnomedicinal practices were from Asian and African regions.
THE AIM OF THE REVIEW: The aim of this review is to summarize the current studies on ethnomedicinal practices, phytochemistry, pharmacological studies and a potential study of Acalypha indica in different locations around the world. This review updates related information regarding the potential therapeutic treatments and also discusses the toxicity issue of Acalypha indica.
MATERIALS AND METHODS: This review was performed through a systematic search related to Acalypha indica including the ethnomedicinal practices, phytochemistry and pharmacological studies around the world. The data was collected from online journals, magazines, and books, all of which were published in English, Malay and Indonesian. Search engine websites such as Google, Google Scholar, PubMed, Science Direct, Researchgate and other online collections were utilized in this review to obtain information.
RESULTS: The links between ethnomedicinal practices and scientific studies have been discussed with a fair justification. Several pharmacological properties exhibited certain potentials based on the obtained results that came from different related studies. Based on literature studies, Acalypha indica has the capability to serve as anthelmintic, anti-inflammation, anti-bacterial, anti-cancer, anti-diabetes, anti-hyperlipidemic, anti-obesity, anti-venom, hepatoprotective, hypoxia, and wound healing medicine. For the traditional practices, the authors also mentioned several benefits of consuming the raw plant and decoction.
CONCLUSION: This review summarizes the current studies of Acalypha indica collected from many regions. This review hopefully will provide a useful and basic knowledge platform for anyone interested in gaining information regarding Acalypha indica.

Matched MeSH terms: Plant Extracts/toxicity
Bioactivity, phytochemistry studies and subacute in vivo toxicity of ethanolic leaf extract of white mulberry (Morus alba linn.) in female mice

Fauzi A, Kifli N, Noor MHM, Hamzah H, Azlan A

J Ethnopharmacol, 2024 May 10;325:117914.
PMID: 38360381 DOI: 10.1016/j.jep.2024.117914

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 β-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

Matched MeSH terms: Plant Extracts/toxicity
Platelet enhancement by Carica papaya L. leaf fractions in cyclophosphamide induced thrombocytopenic rats is due to elevated expression of CD110 receptor on megakaryocytes

Nandini C, Madhunapantula SV, Bovilla VR, Ali M, Mruthunjaya K, Santhepete MN, et al.

J Ethnopharmacol, 2021 Jul 15;275:114074.
PMID: 33831466 DOI: 10.1016/j.jep.2021.114074

ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya leaf juice/decoction has been in use in folk medicine in Srilanka, Malaysia and in few parts of India for enhancing the platelet counts in dengue. In Siddha medicine, a traditional form of medicine in India, papaya leaf juice has been used for increasing the platelet counts. Papaya leaf has been reported to enhance blood volume in ancient Ayurveda books in India. Carica papaya leaf is well known for its platelet enhancement activity. Although many preclinical and clinical studies have demonstrated the ability of papaya leaf juice for platelet enhancement, but the underlying mechanisms are still unclear.
AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp).
MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting.
RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/μL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/μL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats.
CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.

Matched MeSH terms: Plant Extracts/toxicity
Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats

Gupta M, Gulati M, Kapoor B, Kumar B, Kumar R, Kumar R, et al.

J Ethnopharmacol, 2021 Jul 15;275:114115.
PMID: 33852947 DOI: 10.1016/j.jep.2021.114115

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant.
AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta.
MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied.
RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner.
CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

Matched MeSH terms: Plant Extracts/toxicity
Cytotoxicity and inhibition of nitric oxide in lipopolysaccharide induced mammalian cell lines by aqueous extracts of brown seaweed

Jaswir I, Monsur HA, Simsek S, Amid A, Alam Z, bin Salleh MN, et al.

J Oleo Sci, 2014;63(8):787-94.
PMID: 25007746

Aqueous extracts obtained from five Malaysian brown seaweeds, Sargassum duplicatum, Sargassum binderi, Sargassum fulvellum, Padina australis, and Turbinaria turbinata, were investigated for their abilities to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cell lines as well as to determine their chemical composition. The percentage yield of extracts varied among species, with P. australis having the lowest yield and T. turbinata having the highest yield. The chemical compositions of the extracts showed that the percentage of sulfate ions as well as uronic acid and total sugar content varied significantly. All extracts contained high fucose and inhibited NO secretion in a dose-dependent manner. Extracts of P. australis and T. turbinata dosed at 200 μg/mL were able to inhibit NO secretion by > 75%. Furthermore, cytotoxicity assays revealed that some extracts were moderately toxic, while others were not. Based on these results, brown seaweed of Malaysian origin should be investigated for the production of additional anti-inflammatory compounds.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Optimization and Characterization of Palm Oil-based Nanoemulsion Loaded with Parthenium hysterophorus Crude Extract for Natural Herbicide Formulation

Zainuddin NJ, Ashari SE, Salim N, Asib N, Omar D, Lian GEC

J Oleo Sci, 2019 Aug 01;68(8):747-757.
PMID: 31292338 DOI: 10.5650/jos.ess18209

The present study revealed the optimization of nanoemulsion containing palm oil derivatives and Parthenium hysterophorus L. crude extract (PHCE) as pre-emergence herbicide formulation against Diodia ocimifolia. The nanoemulsion formulation was prepared by high energy emulsification method, and it was optimized by mixture experimental design (MED). From the optimization process, analysis of variance (ANOVA) showed a fit quadratic polynomial model with an optimal formulation composition containing 30.91% of palm kernel oil ester (PKOE), 28.48% of mixed surfactants (Tensiofix and Tween 80, 8:2), 28.32% of water and 12.29% of PHCE. The reading of both experimental and predicted particle size in the verification experiment were acceptable with a residual standard error (RSE) was less than 2%. Under the optimal condition, the smallest particle size obtained was 140.10 nm, and the particle was shown by morphology analysis to be spherical and demonstrated good stability (no phase separation) under centrifugation and different storage conditions (25 ± 5°C and 45°C). Nanoemulsion stored for 60 days exhibits monodisperse emulsion with a slight increase of particle size. The increase in particle size over time might have contributed by Ostwald ripening phenomenon which is shown by a linear graph from Ostwald ripening rate analysis. In the in vitro germination test, P. hysterophorus nanoemulsion (PHNE) was shown to cause total inhibition of D. ocimifolia seed at lower concentration (5 g L-1) as compared to PHCE (10 g L-1). The finding of the research could potentially serve as a platform for the development of palm oil based formulation containing plant crude extract for green weed management.

Matched MeSH terms: Plant Extracts/toxicity*
Investigations into the therapeutic effects of aerial and stem parts of Buxus papillosa C.K. Schneid.: In vitro chemical, biological and toxicological perspectives

Saleem H, Htar TT, Naidu R, Ahmad I, Zengin G, Ahmad M, et al.

J Pharm Biomed Anal, 2019 Mar 20;166:128-138.
PMID: 30640043 DOI: 10.1016/j.jpba.2019.01.007

In this study, different solvent extracts (methanol, dichloromethane and n-hexane) from aerial and stem parts of Buxus papillosa C.K. Schneid (Buxaceae) were investigated for a panoply of bioassays. Biological profiles were established by determining antioxidant and enzyme inhibition profiles. Toxicity was tested using MTT cell viability assay on five different human cancer cell lines i.e, MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480. For chemical fingerprinting, total bioactive contents and UHPLC-MS secondary metabolites profile were determined. Generally, both aerial and stem methanol extracts had highest total bioactive contents, radical scavenging and reducing power potential. DCM and n-hexane extracts were found to be most active for total antioxidant and metal chelating activity. The UHPLC-MS analysis of methanol extracts revealed the presence of several phenolic, flavonoid, alkaloid, saponin and depsipeptide derivatives. All the extracts were significantly active against butyrylcholinesterase, whereas moderate inhibition was observed for acetylcholinesterase, α-glucosidase and urease. Similarly, a considerable level of cytotoxicity was observed against all the tested cell lines with IC50 values ranging from 26 to 225.9 μg/mL. Aerial methanol and stem n-hexane extracts were found to be most cytotoxic. Principal component analysis was also performed to find any possible correlation between biological activities and total bioactive contents. On the basis of our findings, B. papillosa may be considered as promising source of bioactive molecules.

Matched MeSH terms: Plant Extracts/toxicity*
Functional Validation of DownRegulated MicroRNAs in HeLa Cells Treated with Polyalthia longifolia Leaf Extract Using Different Microscopic Approaches: A Morphological Alteration-Based Validation

Shanmugapriya, Vijayarathna S, Sasidharan S

Microsc Microanal, 2019 10;25(5):1263-1272.
PMID: 31383043 DOI: 10.1017/S1431927619014776

Several microscopy methods have been developed to assess the morphological changes in cells in the investigations of the mode of cell death in response to a stimulus. Our recent finding on the treatment of the IC50 concentration (26.67 μg/mL) of Polyalthia longifolia leaf extract indicated the induction of apoptotic cell death via the regulation of miRNA in HeLa cells. Hence, the current study was conducted to validate the function of these downregulated microRNAs in P. longifolia-treated HeLa cells using microscopic approaches. These include scanning electron microscope (SEM), transmission electron microscope (TEM), and acridine orange/propidium iodide (AO/PI)-based fluorescent microscopy techniques by observing the morphological alterations to cells after transfection with mimic miRNA. Interestingly, the morphological changes observed in this study demonstrated the apoptotic hallmarks, for instance, cell blebbing, cell shrinkage, cytoplasmic and nuclear condensation, vacuolization, cytoplasmic extrusion, and the formation of apoptotic bodies, which proved the role of dysregulated miRNAs in apoptotic HeLa cell death after treatment with the P. longifolia leaf extract. Conclusively, the current study proved the crucial role of downregulated miR-484 and miR-221-5p in the induction of apoptotic cell death in P. longifolia-treated HeLa cells using three approaches-SEM, TEM, and AO/PI-based fluorescent microscope.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Acuminatol and other antioxidative resveratrol oligomers from the stem bark of Shorea acuminata

Muhammad N, Din LB, Sahidin I, Hashim SF, Ibrahim N, Zakaria Z, et al.

Molecules, 2012 Jul 30;17(8):9043-55.
PMID: 22847143 DOI: 10.3390/molecules17089043

A new resveratrol dimer, acuminatol (1), was isolated along with five known compounds from the acetone extract of the stem bark of Shorea acuminata. Their structures and stereochemistry were determined by spectroscopic methods, which included the extensive use of 2D NMR techniques. All isolated compounds were evaluated for their antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (RSA) and the β-carotene-linoleic acid (BCLA) assays, and compared with those of the standards of ascorbic acid (AscA) and butylated hydroxytoluene (BHT). All compounds tested exhibited good to moderate antioxidant activity in the DPPH assay (IC₅₀s 0.84 to 10.06 mM) and displayed strong inhibition of β-carotene oxidation (IC₅₀s 0.10 to 0.22 mM). The isolated compounds were evaluated on the Vero cell line and were found to be non-cytotoxic with LC₅₀ values between 161 to 830 µM.

Matched MeSH terms: Plant Extracts/toxicity
Fulltext Genotoxicity of Euphorbia hirta: an Allium cepa assay

Yuet Ping K, Darah I, Yusuf UK, Yeng C, Sasidharan S

Molecules, 2012 Jun 26;17(7):7782-91.
PMID: 22735780 DOI: 10.3390/molecules17077782

The potential genotoxic effects of methanolic extracts of Euphorbia hirta which is commonly used in traditional medicine to treat a variety of diseased conditions including asthma, coughs, diarrhea and dysentery was investigated using Allium cepa assay. The extracts of 125, 250, 500 and 1,000 µg/mL were tested on root meristems of A. cepa. Ethylmethanesulfonate was used as positive control and distilled water was used as negative control. The result showed that mitotic index decreased as the concentrations of E. hirta extract increased. A dose-dependent increase of chromosome aberrations was also observed. Abnormalities scored were stickiness, c-mitosis, bridges and vagrant chromosomes. Micronucleated cells were also observed at interphase. Result of this study confirmed that the methanol extracts of E. hirta exerted significant genotoxic and mitodepressive effects at 1,000 µg/mL.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Corn silk (Stigma maydis) in healthcare: a phytochemical and pharmacological review

Hasanudin K, Hashim P, Mustafa S

Molecules, 2012 Aug 13;17(8):9697-715.
PMID: 22890173 DOI: 10.3390/molecules17089697

Corn silk (Stigma maydis) is an important herb used traditionally by the Chinese, and Native Americans to treat many diseases. It is also used as traditional medicine in many parts of the world such as Turkey, United States and France. Its potential antioxidant and healthcare applications as diuretic agent, in hyperglycemia reduction, as anti-depressant and anti-fatigue use have been claimed in several reports. Other uses of corn silk include teas and supplements to treat urinary related problems. The potential use is very much related to its properties and mechanism of action of its plant's bioactive constituents such as flavonoids and terpenoids. As such, this review will cover the research findings on the potential applications of corn silk in healthcare which include its phytochemical and pharmacological activities. In addition, the botanical description and its toxicological studies are also included.

Matched MeSH terms: Plant Extracts/toxicity
Fulltext Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats

Afzan A, Abdullah NR, Halim SZ, Rashid BA, Semail RH, Abdullah N, et al.

Molecules, 2012 Apr 10;17(4):4326-42.
PMID: 22491681 DOI: 10.3390/molecules17044326

Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Acute oral toxicity of methanolic seed extract of Cassia fistula in mice

Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY, Sasidharan S

Molecules, 2011 Jun 23;16(6):5268-82.
PMID: 21701437 DOI: 10.3390/molecules16065268

BACKGROUND AND OBJECTIVE: Cassia fistula is widely used in traditional medicine to treat various types of ailments. The evaluation of toxic properties of C. fistula is crucial when considering public health protection because exposure to plant extracts can result in undesirable effects on consumers. Hence, in this study the acute oral toxicity of C. fistula seeds extract was investigated in mice.
RESULTS: Oral administration of crude extract at the highest dose of 5000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that C. fistula in nontoxic. Throughout 14 days of the treatment no changes in behavioural pattern, clinical sign and body weight of mice in both control and treatment groups. Also there were no any significant elevations observed in the biochemical analysis of the blood serum. Further, histopathological examination revealed normal architecture and no significant adverse effects observed on the kidney, heart, liver, lung and spleen.
CONCLUSIONS: Overall, the results suggest that, the oral administration of C. fistula methanolic seeds extract did not produce any significant toxic effect in mice. Hence, the extract can be utilized for pharmaceutical formulations.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Phytochemical and cytotoxic investigations of Curcuma mangga rhizomes

Malek SN, Lee GS, Hong SL, Yaacob H, Wahab NA, Faizal Weber JF, et al.

Molecules, 2011 May 31;16(6):4539-48.
PMID: 21629182 DOI: 10.3390/molecules16064539

Investigations on the cytotoxic effects of the crude methanol and fractionated extracts (hexane, ethyl acetate) C. mangga against six human cancer cell lines, namely the hormone-dependent breast cell line (MCF-7), nasopharyngeal epidermoid cell line (KB), lung cell line (A549), cervical cell line (Ca Ski), colon cell lines (HCT 116 and HT-29), and one non-cancer human fibroblast cell line (MRC-5) were conducted using an in-vitro neutral red cytotoxicity assay. The crude methanol and fractionated extracts (hexane and ethyl acetate) displayed good cytotoxic effects against MCF-7, KB, A549, Ca Ski and HT-29 cell lines, but exerted no damage on the MRC-5 line. Chemical investigation from the hexane and ethyl acetate fractions resulted in the isolation of seven pure compounds, namely (E)-labda-8(17),12-dien-15,16-dial (1), (E)-15,16-bisnor-labda-8(17),11-dien-13-on (2), zerumin A (3), β-sitosterol, curcumin, demethoxycurcumin and bis-demethoxycurcumin. Compounds 1 and 3 exhibited high cytotoxic effects against all six selected cancer cell lines, while compounds 2 showed no anti-proliferative activity on the tested cell lines. Compound 1 also demonstrated strong cytotoxicity against the normal cell line MRC-5. This paper reports for the first time the cytotoxic activities of C. mangga extracts on KB, A549, Ca Ski, HT-29 and MRC-5, and the occurrence of compound 2 and 3 in C. mangga.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb

Devaraj S, Esfahani AS, Ismail S, Ramanathan S, Yam MF

Molecules, 2010 Apr;15(4):2925-34.
PMID: 20428088 DOI: 10.3390/molecules15042925

Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P < 0.05) suppressed the paw licking time of rats in both early and late phases at doses 200 and 400 mg/kg of the extract, respectively. In the acute oral toxicity study, Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.

Matched MeSH terms: Plant Extracts/toxicity
Fulltext Mosquitocidal and Oviposition Repellent Activities of the Extracts of Seaweed Bryopsis pennata on Aedes aegypti and Aedes albopictus

Yu KX, Wong CL, Ahmad R, Jantan I

Molecules, 2015;20(8):14082-102.
PMID: 26247928 DOI: 10.3390/molecules200814082

The ever-increasing threat from infectious diseases and the development of insecticide resistance in mosquito populations drive the global search for new natural insecticides. The aims of this study were to evaluate the mosquitocidal activity of the extracts of seaweed Bryopsis pennata against dengue vectors Aedes aegypti and Aedes albopictus, and determine the seaweed's toxic effect on brine shrimp nauplii (as a non-target organism). In addition, the chemical compositions of the active larvicidal extract and fraction were analyzed by using liquid chromatography-mass spectrometry (LC-MS). Chloroform extract exhibited strong ovicidal activity (with LC50 values of 229.3 and 250.5 µg/mL) and larvicidal activity against Ae. aegypti and Ae. albopictus. The larvicidal potential of chloroform extract was further ascertained when its A7 fraction exhibited strong toxic effect against Ae. aegypti (LC50 = 4.7 µg/mL) and Ae. albopictus (LC50 = 5.3 µg/mL). LC-MS analysis of the chloroform extract gave a tentative identification of 13 compounds; Bis-(3-oxoundecyl) tetrasulfide was identified as the major compound in A7 fraction. Methanol extract showed strong repellent effect against female oviposition, along with weak adulticidal activity against mosquito and weak toxicity against brine shrimp nauplii. The mosquitocidal results of B. pennata suggest further investigation for the development of effective insecticide.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext In Vitro and In Vivo Anticancer Activity of the Most Cytotoxic Fraction of Pistachio Hull Extract in Breast Cancer

Seifaddinipour M, Farghadani R, Namvar F, Bin Mohamad J, Muhamad NA

Molecules, 2020 Apr 13;25(8).
PMID: 32295069 DOI: 10.3390/molecules25081776

Pistacia (Pistacia vera) hulls (PV) is a health product that has been determined to contain bioactive phytochemicals which have fundamental importance for biomedical use. In this study, PV ethyl acetate extraction (PV-EA) fractions were evaluated with the use of an MTT assay to find the most cytotoxic fraction, which was found to be F13b1/PV-EA. After that, HPTLC was used for identify the most active compounds. The antioxidant activity was analyzed with DPPH and ABTS tests. Apoptosis induction in MCF-7 cells by F13b1/PV-EA was validated via flow cytometry analysis and a distinctive nuclear staining method. The representation of genes like Caspase 3, Caspase 8, Bax, Bcl-2, CAT and SOD was assessed via a reverse transcription (RT_PCR) method. Inhabitation of Tubo breast cancer cell development was examined in the BALB-neuT mouse with histopathology observations. The most abundant active components available in our extract were gallic acid and the flavonoid quercetin. The F13b1/PV-EA has antiradical activity evidence by its inhibition of ABTS and DPPH free radicals. F13b1/PV-EA displayed against MCF-7 a suppressive effect with an IC50 value of 15.2 ± 1.35 µg/mL. Also, the expression of CAT, SOD, Caspase 3, Caspase 8 and Bax increased and the expression of Bcl-2 decreased. F13b1/PV-EA dose-dependently inhibited tumor development in cancer-induced mice. Thus, this finding introduces F13b1/PV-EA as an effectual apoptosis and antitumor active agent against breast cancer.

Matched MeSH terms: Plant Extracts/toxicity
Fulltext Hematological, Biochemical, Histopathological and ¹H-NMR Metabolomics Application in Acute Toxicity Evaluation of Clinacanthus nutans Water Leaf Extract

Khoo LW, Foong Kow AS, Maulidiani M, Lee MT, Tan CP, Shaari K, et al.

Molecules, 2018 Aug 29;23(9).
PMID: 30158427 DOI: 10.3390/molecules23092172

The present study aims for the first time to provide the in vivo acute toxicological profile of the highest dose of Clinacanthus nutans (Burm. f.) Lindau water leaf extract according to the Organization for economic co-operation and development (OECD) 423 guidelines through conventional toxicity and advanced proton nuclear magnetic resonance (¹H-NMR) serum and urinary metabolomics evaluation methods. A single dose of 5000 mg/kg bw of C. nutans water extract was administered to Sprague Dawley rats, and they were observed for 14 days. Conventional toxicity evaluation methods (physical observation, body and organ weight, food and water consumption, hematology, biochemical testing and histopathological analysis) suggested no abnormal toxicity signs. Serum ¹H-NMR metabolome revealed no significant metabolic difference between untreated and treated groups. Urinary ¹H-NMR analysis, on the other hand, revealed alteration in carbohydrate metabolism, energy metabolism and amino acid metabolism in extract-treated rats after 2 h of extract administration, but the metabolic expression collected after 24 h and at Day 5, Day 10 and Day 15 indicated that the extract-treated rats did not accumulate any toxicity biomarkers. Importantly, the outcomes further suggest that single oral administration of up to 5000 mg/kg bw of C. nutans water leaf extract is safe for consumption.

Matched MeSH terms: Plant Extracts/toxicity*
Fulltext Acute oral toxicity and brine shrimp lethality of Elaeis guineensis Jacq., (oil palm leaf) methanol extract

Syahmi AR, Vijayarathna S, Sasidharan S, Latha LY, Kwan YP, Lau YL, et al.

Molecules, 2010 Nov 10;15(11):8111-21.
PMID: 21072022 DOI: 10.3390/molecules15118111

Elaeis guineensis (Arecaceae) is widely used in West African traditional medicine for treating various ailments. An evaluation on the toxicity of extracts of this plant is crucial to support the therapeutic claims. The acute oral toxicity and brine shrimp lethality of a methanolic extract of this plant was tested. Oral administration of crude extract at the highest dose of 5,000 mg/kg resulted in no mortalities or evidence of adverse effects, implying that E. guineensis is nontoxic. Normal behavioral pattern, clinical signs and histology of vital organs confirm this evidence. The E. guineensis extracts screened for toxicity against brine shrimp had 50% lethal concentration (LC₅₀) values of more than 1.0 mg/mL (9.00 and 3.87 mg/mL, at 6 and 24 h, respectively), confirming that the extract was not toxic. Maximum mortalities occurred at 100 mg/mL concentration while the least mortalities happened to be at 0.195 mg/mL concentration. The results of both tests confirm that E. guineensis is nontoxic and hence safe for commercial utilization.

Matched MeSH terms: Plant Extracts/toxicity*
Xanthones from Garcinia mangostana (Guttiferae)

Ee GC, Daud S, Taufiq-Yap YH, Ismail NH, Rahmani M

Nat Prod Res, 2006 Oct;20(12):1067-73.
PMID: 17127660

Studies on the stem of Garcinia mangostana have led to the isolation of one new xanthone mangosharin (1) (2,6-dihydroxy-8-methoxy-5-(3-methylbut-2-enyl)-xanthone) and six other prenylated xanthones, alpha-mangostin (2), beta-mangostin (3), garcinone D (4), 1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone (5), mangostanol (6) and 5,9-dihydroxy-8- methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyrano-[3,2-b]-xanthene-6-one (7). The structures of these compounds were determined by spectroscopic methods such as 1H NMR, 13C NMR, mass spectrometry (MS) and by comparison with previous studies. All the crude extracts when screened for their larvicidal activities indicated very good toxicity against the larvae of Aedes aegypti. This article reports the isolation and identification of the above compounds as well as bioassay data for the crude extracts. These bioassay data have not been reported before.

Matched MeSH terms: Plant Extracts/toxicity

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