Table 2.
Active ingredients and toxicological evaluation of the medicinal plants given in Table 1.
| S. No | Names | Active ingredients | Toxicological evaluation |
|---|---|---|---|
| 1 | Allium cepa | Quercetin, N-acetylcysteine, alliuocide, cycloalliin, S-methyl-L-cysteine, S-propyl-L-cysteine, sulfoxide, dimethyl trisulfide, S-methyl-L-cysteine sulfoxide [128] | The animals tested were found healthy with no sign of toxicity up to the dose of 2 500 mg/kg. However, at 5 000 mg/kg, animals were weak and had intense extreme tachycardia and disorientation but no death was recorded. Thus, LD50 was more than 5 000 mg/kg [129]. |
| 2 | Anthemis herba alba | Guainalides, eudesmanolide, pseudogua inolides, xanthonolides, flavone, flavonol glycosides, hispidulin, cirsilineol, vicenin-2, schaftoside, isoschaftoside, 5′,4-dihydroxy-6,7,3-trimethoxyflavone, quercetin-3-rutinoside, patuletin 3-rutinoside, patuletin 3-glucoside [130] | The available toxicological investigations have shown generally that Anthemis herba-alba is free from toxic effects at the different doses used in the studies [130] |
| 3 | Cichorium intybus | Chicoric acid, inulin, cichoralexin, cichoriin, esculetin, isochlorogenic acid, chlorogenic acid, caffeic acid, dicaffeoylquinic acid, aesculin, arginine, histidine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, threonine, valine, serine, glutamic acid, glycine, alanine, aspartic acid, and proline [44, 45] | There were no treatment-related toxic effects from chicory extract administered orally at 70, 350, or 1000 mg/kg/day. There were no observed adverse effects of chicory extract in these studies [45] |
| 4 | Clitoria ternatea | Kaempferol, quercetin, myricetin, taxaxerol, tannic acid, 3-monoglucoside, β-sitosterol, delphinidin-3,5-diglucoside, anthoxanthin glucoside, p-hydroxycinnamic acid, kaempferol 3-neohesperidoside, myricetin 3-rutinoside, hexacosanol [48] | Ethanolic extract of aerial parts and root of CT led to lethargy in mice at the doses of 1500 mg/kg and above, orally [31]. Ptosis was seen above 2000 mg/kg dose in mice. Through intraperitoneal route, 2900 mg/kg dose was lethal within 6 hr due to severe CNS depression [47]. |
| 5 | Ficus carica | Over 100 bioactive compounds have been identified in fig such as rutin, arabinose, chlorogenic acid, β-amyrins, syringic acid, β-carotenes, glycosides, β-sitosterols, and xanthotoxol [131] | The rats tested were found healthy with no sign of toxicity up to the dose of 5000, 5500, and 6000 mg/kg. However, at 5 000 mg/kg, animals were weak and had intense extreme tachycardia and disorientation but no death was recorded. Thus, LD50 was more than 6000 mg/kg [132] |
| 6 | Ficus benghalensis | Leucopelargonidin-3-0-α-L rhamnoside, eucodelphinidin, leucoanthocyanidia, leucoanthocyanin, α-amyrin acetate [53] | In acute toxicity studies, no mortality and signs of toxicity were observed at the dose of 2000 and 5000 mg/kg body weight for aqueous and ethanol extracts, respectively [53] |
| 7 | Ficus religiosa | Lupeol, β-sitosterol, β-sitosterol-d-glucoside, stigmasterol, lanosterol, campesterol, octacosanol, methyl oleonate, lupen-3-one, bergapten, and bergaptol [53] | Acute toxicity reported up to dose level 2000 mg/kg showed no mortality [53] |
| 8 | Ficus microcarpa | Polyphenols, organic acids, alkaloids, polysaccharides, megastigmanes, pheophytins, catechin, epicatechin, isovitexin, phenolic acids [53] | The oral administration of a single dose of 2000 mg/kg ethanol or methanol extract of leaves showed no mortality or behavioral alterations in the tested animals [53] |
| 9 | Hypericum perforatum | Quercitrin, rutin, hypericin, kaempferol, biapigenin, hyperforin [133] | Acute toxicity studies revealed the nontoxic nature of the H. perforatum [55] |
| 10 | Anethum graveolens | Carvone, α-phellandrene, limonene, dill ether, myristicin coumarins, flavonoids, phenolic acids, steroids [134] | The mice treated with AG of different doses of 1000, 2000, 3000, 4000, and 5000 mg/kg of body showed no toxicity [135] |
| 11 | Cuminum cyminum | Cuminaldehyde, limonene, α- and β-pinene, 1, 8-cineole, o-and p-cymene, α- and γ-terpinene, safranal, and linalool [58, 59] | The acute lethal toxicity test revealed that cumin crude extract was very safe [58] |
| 12 | Marrubium vulgare | Furanic labdane diterpenes, marrubenol, marrubiin, ladanein [60] | An acute toxicity study of M. vulgare (1 g/kg) extract orally administered at a dose of 1 g/kg body weight to the mice and treated mice showed tachycardia 1 h after intake of the infusion and loss of appetite 3 h after intake of the infusion. In another experiment, a single dose of 2000 mg/kg extract of M. vulgare for an acute toxicity study showed no toxicity [60]. |
| 13 | Mentha longifolia | Lucenin-1, lucenin-2, camphelinone, camphene, carveol, carvone, carvone oxide, limonene, linalool, menthatriene, menthofuran, menthol, menthone, myrcene, p-cymene, piperitenone, piperitone, sabinene, α-pinene, α-terpinene, α-terpineol, longifone, pulegone, longifoamide-A, longifoamide-B, longiside-A, longiside-B, eugenol, salvianolic acid, eriodictyol-7-rutinoside, apigenin-7-O-glucoside, hypolaetin, longitin, luteolin, etc. [136] | M. longifolia extract was safe, and no toxicity or mortality was observed in both the oral (3200 mg/kg) and intraperitoneal (1730 mg/kg) administration in rats. Fourteen days of oral administration of the essential oil (125, 250, 375, and 500 µL/kg) resulted in the reduction of red blood cells and lymphocytes and elevation of neutrophils and monocytes compared with normal animals [136]. |
| 14 | Origanum syriacum | Carvacrol, thymol, thymoquinone [137] | Not available |
| 15 | Teucrium oliverianum | 8-O-acetylharpagide, 12-O-methylteucrolin A, teucrolivin A, eupatorin, teucrolivin B, μ24(S)-stigmasta-5,22,25-trin-3β-ol [66] | Not available |
| 16 | Teucrium polium | Apigenin, luteolin, rutin, cirsiliol, cirsimaritin, salvigenin, and eupatorin in the roots, aerial parts, and inflorescences, teucardoside, b-sitosterol, stigmasterol, campesterol, brassicasterol, and clerosterol [68] | All rats treated with different concentrations of the total extract of TP were alive during the 14 days of observation. The animals did not show visible signs of acute toxicity. It suggested that the LD50 of the total extract was higher than 8 g/kg [138] |
| 17 | Achyranthes aspera | Aliphatic acid, betaine, achyranthine, β-ecdysterone, achyranthes saponins A, B, C, D, oleonolic acid, glycosides, triacontanol, E-sitosterol and spinasterol, triacontanol, hydroquinone, eugenol [70] | In acute oral toxicity studies, there was no increase or decrease in any of the parameters studied, in comparison with control animals [139] |
| 18 | Aerva lanata | Quercetin, betulin, aervine, ervoside, methylervine, aervine, lupeol, kaempferol, aervolanine, aervolanine, ervoside, methylaervine, persinosides A and B, tannic acid, lupeol acetate, benzoic acid, methyl grevillate [140] | The LD50 of the extract of AL for oral and IP acute toxicity tests were 22.62 g/kg and 0.432 g/kg, respectively. The extract produced apparent changes in body weights of both male and female rats and increased the weights of lung, brain, and pancreas of female rats while reducing the weight of testes in male rats. Hematological parameters were also altered [72] |
| 19 | Alternanthera sessilis | Stigmasterol, β-sitosterol, β-carotene, ricinoleic acid, myristic, palmitic, stearic, oleic, and linoleic acids, α-spiraterol, uronic acid, cyclo eucalenol, choline, oleanolic acid, lupeol [141] | The crude extract did not show any toxicity in mice even at the highest dose tested [75] |
| 20 | Carissa edulis | Β-Amyrin, (+)-carissone, 2α-carissanol, 6α-carissanol, dehydrocarissone, pinene, myrcene, limonene, sabanene, rutin, epicatechin gallate, carinol, lariciresinol, β-sitosterol, sitosterol glucoside, stigmasterol glucoside, scopoletin, isofraxidin, pinitol [77] | Lethal effects were not observed after the oral administration of the standardized ethanol extract at doses of 1600, 2900, and 5000 mg/kg. No behavioral changes were observed during the observation period. The oral LD50 of the extract was estimated to be greater than 5000 mg/kg. [142]. |
| 21 | Catharanthus roseus | Vinblastine, vincristine, vindesine, vindeline tabersonine, ajmalicine, vinceine, vineamine, raubasin, reserpine, catharanthine, rosindin [143] | No mortality, but dose level higher than 300 mg of C. roseus extract can produce signs of biochemical and histopathological toxicity in liver, kidney, and heart. It is recommended that lower doses than the studied ones should be used for treatment [144] |
| 22 | Rhazya stricta | Polyneuridine, stemmadenine, strictanol, rhazimine, rhazinilam, rhazimanine, sewarine, vallesiachotamine, tetrahydrosecamine [145] | Daily oral dosing of R. stricta extract (0.25 g/kg) for 42 days was not fatal to sheep [145]. |
| 23 | Calotropis procera | Calotropin, calotoxin, calactin, uscharin, voruscharin, uzarigenin, syriogenin, proceroside, calotropagenin, calotropain enzymes, α-amyrin, β-amyrin, lupeol, β-sitosterol, ursolic acid, calotropin, gigantin, giganteol [146] | 2000 mg/kg body weight in single oral administration of aqueous and hydroalcoholic extract did not cause any death after 72 h post-treatment in male and female mice. Daily administration of aqueous extract to male and female Wistar rats during 3 and 6 weeks at the dose of 20 mg/kg/day induced no mortality in either sex [147]. Whoever C. procera is a toxic plant that is avoided by grazing animals. Its latex is used by tribes to poison arrows used for hunting. If in contact with human eye, it could cause ocular toxicity, causing loss of vision and photophobia [146] |
| 24 | Opuntia dillenii | Betanin, betanidin, kaempferol, kaempferide, quercetin, isorhamnetin, β-sitosterol, C29-5β-sterols, taraxerol, friedelin, methyl linoleate, 7-oxositosterol, 6β-hydroxystigmast-4-ene-3-one, daucosterol, methyl eucomate, eucomic acid [85] | During the oral toxicity study of the crude drug in rats, given doses up to 50 ml/kg exhibited no symptoms of toxicity [85] |
| 25 | Opuntia ficus indica | Quercetin, isorhamnetin, kaempferol, luteolin, isorhamnetin, isorhamnetin glycosides, gallic acid, coumaric, narcissin, rutin, nicotiflorin, isoquercetin, ferulic acid [87]. | In vivo toxicity study suggests that the oral administration of Opuntia ficus indica extract at levels up to 2000 mg/kg/day does not cause adverse effects in male and female rats [148]. |
| 26 | Capparis decidua | n-Triacontane, n-pentacosane, β-carotene, n-triacontanol, kaempferol, quercetin, isodulcite, nanocosane, capric acid, glucocapparin, capparine, capparinine, cappariline, codonocarpin, β-sitosterol [88] | The oral administration of C. decidua extract (500, 1000, 2000, and 4000 mg/kg) did not provoke any gross behavioral changes or manifestations of toxic symptoms in male rats [149]. |
| 27 | Beta vulgaris | Betaine, betacyanins, betaxanthins, oxalic acid, and ascorbic acid [89] | In acute oral toxicity studies, the BVBF did not show any sign and symptoms of toxicity and mortality up to 2000 mg/kg dose, considered relatively safe [150] |
| 28 | Haloxylon salicorlicum Bunge | Kaempferol, quercetin, betaine chloride, piperidine, anabasine, aldotripiperideine, haloxine, halosaline, oxedrine, tyramine, N-methyltyramine, scopoletin, scopolin, umbelliferone, xanthotoxol, isooxyimperatorin, esculetin, β-sitosterol, ursolic acid, β-amyrin [93]. | H. salicorlicum extract at doses 0.1, 0.2, 0.3, 0.4, and 0.5 mL/kg orally administered in rats was safe and showed no mortality or adverse effect [92]. |
| 29 | Evolvulus alsinoides | β-Sitosterol, betaine, shankpushpin, evolvine, caffeic acid, 6-methoxy-7-O-β-glucopyranoside coumarin, 2-C-methyl erythritol, kaempferol-7-O-β-glucopyranoside, kaempferol-3-O-β-glucopyranoside, quercetin-3-O-β-glucopyranoside, scopoletin, scopolin [151] | The Evolvulus alsinoides extract did not cause any mortality up to a dose of 1500 mg/kg body weight and no behavioral, neurological, and autonomic profiles and was found to be safe [151]. |
| 30 | Ipomea aquatica | Caffeic acid, chlorogenic acid, quercetin glucoside, quercetin malonyl glucoside, quercetin diglucoside, catechin, isochlorogenic acid A, C, aspartic acid, glycine, alanine and leucine, 7-O-β-D-glucopyranosyldihydroquercetin-3-O-α-D-glucopyranoside [97, 98] | In acute toxicity studies, I. aquatica extract was found to be safe up to 2g to 5 g/kg in mice. No mortality or toxic symptoms were observed during the entire duration of the study [152, 153]. |
| 31 | Citrullus colocynthis | Cucurbitane, gallic acid, kaempferol, cucurbitacin A-E, I-L, chlorogenic acid, caffeic acid, colocynthoside A,B,C; choline, almitic acid, stearic acid, linoleic acid, oleic acids, catechin, myricetin, α-tocopherol, γ-tocopherol, β-carotene [153] | C. colocynthis plant is safe to use. Studies showed that lethal dose (LD50) to be 200 mg/kg, which indicate that the studied plant is not toxic when comparing the LD50 values of most bioactive pharmaceuticals currently used in therapeutics [154] |
| 32 | Citrullus lanatus | Lycopene, vitamin A, cucurbitacin E, citrulline arginine, glutamine and aspartic acid, pectin, vitamin b-complex and minerals [155, 156] | In acute toxicity study, there was no mortality observed up to the maximum dose level of 2000 mg/kg body weight of the extract after administered orally [102] |
| 33 | Coccinia grandis | Cephalandrol, β-sitosterol, cephalandrins A and B, β-amyrin acetate, lupeol, cucurbitacin B, taraxerone, taraxerol, β-carotene, lycopene, cryptoxanthin, xyloglucan, carotenoids, β-sitosterol, stigma-7-en-3-one, lupeol, β-amyrin, β-sitosterol, taraxerol [157] | The acute toxicity study indicated that treatment of C. grandis is safe up to 2 g/kg tested on animal [158]. |
| 34 | Jatropha curcas | Jatrophol, jatropha factor C1, C2, C3,C4, C5, C6, jatropholones A, B, palmarumycin CP1, JC1, JCV2, curcin, curcacycline A, curcain, β-amyrin, β-sitosterol, stigmasterol, friedelin, taraxasterol, diamide, pyrimidine-2,4-dione, nobiletin, tomentin [103] | Many researchers have confirmed that J. curcas is highly toxic for animal as well as human. All parts of J. curcas are toxic and toxic compound reported from this plant like lectins, curcin, phorbol esters, phytate, protease inhibitors [103] |
| 35 | Ricinus communis | Rutin, quercetin, gallic acid, ricin, ricin A, kaempferol-3-O-β rutinoside, gentistic acid, linolenic acid, α-pinene, α-thujone, stigmasterol, ricinine, β-sitosterol, lupeol, castor oil [159, 160] | R. communis extracts given by oral route were safe up to a dose of 2,000 mg/kg/BW and did not show any mortality and toxic effects in the behavior of the treated animals [104]. |
| 36 | Ficus carica | Ferulic acid, quercetin-3-O-glucoside, quercetin-3-O-rutinoside, psoralen, bergapten, coumarin, oleanolic acid, eugenol, angelicin, germacrene D, menthol, α-pinene, β-pinene [161] | Toxicity of 70% methanolic extract of Ficus carica leaves showed LD50 value of brine shrimp assay was 0.158 mg/ml [162] |
| 37 | Ficus sycomorus | Tannins, saponins, flavones, aglycones, anthraquinone glycosides, and flavonoid glycosides [53] | F. sycomorus methanol extract of stem bark is nontoxic up to the dose of 5000 mg/kg [53] |
| 38 | Sesamum indicum | Thelignans, sesamolin, sesamin, pinoresinol, lariciresinol, α-globulin, β-globulin, triacylglycerols, oleic, linoleic acids, sesamol, γ-tocopherol, 2-furfurylthiol, 2-phenylethylthiol, 2-methoxyphenol, 2-pentylpyridine, vitamin E, quinone, sesangolin [163, 164] | S. indicum ethanol extract is safe, up to dose level of 2000 mg/kg in acute toxicity studies in tested animals [165] |
| 39 | Plantago ovata | Hemicellulose,d-xylose, l-arabinose, d-glucose, d-galactose, and l-rhamnose, 5, 6,8-epiloganic acid, gardoside, plantamajoside [166] | 4,5 Gram seed husk one to four times a day soaked in 150 ml of warm water recommend by WHO. Studies confirmed its side effect like bloating, gas, and allergy. No mortality reported [167] |
| 40 | Polygala erioptera | Helioxanthin [168]. No literature available. Recommended for natural products, isolation, biological and toxicological evaluation. | No literature available. Recommended for pharmacological and toxicological evaluation. |
| 41 | Polygonum aviculare L | Protocatechuic acid, catechin, myricitrin, epicatechin-3-O-gallate, avicularin, quercetin, juglanin, kaempferol, myricetin 3-0-(3′-0-galloyl-rhamnopyranoside, cinaroside, liquiritin, rutin [169, 170] | No data available |
| 42 | Ziziphus spina-christi | Jujuboside B1, christinin A, christinin A1 and A2, lotoside II, catechin, epicatechin, kaempferol 3-O-(6-O-rhamnosyl-galactoside), quercetin 7-O-(6-O-rhamnosyl-glucoside), quercetin 3-O-glucoside, kaempferol 3-O-glucoside [171, 172] | Butanol and water extract of Ziziphus spina-christi up to 100 mg/kg and 5 g/kg, respectively, in animal model produced no functional or structural disturbances in liver and kidney and no hematological changes [173, 174] |
| 43 | Bacopa monnieri | Bromine, β-sitosterol, betulinic acid, stigmasterol nicotinine, herpestine, bacosides A, bacopasides (I, II, III, IV, V), pseudojujubogenin glycoside, saponins (A, B, C) [175] | B. monnieri extract at the dose of 5,000 mg/kg did not cause any side effects. Similarly doses of 30, 60, 300, and 1,500 mg/kg given for 270 days did not produce any toxicity in rats [176]. |
| 44 | Lycium shawii | Lyciumate, cyclopentapyrrolidine, imidazole, piperidine, nortropane, tropane, pyrrole, spermine, costunolide, catechin, lyciumaside, emodin, betulinic acid, β-sitosterol glucopyranoside, quercetin, gallic acid, rutin, ρ-coumaric acid, ferulic acid [177, 178] | Reported data revealed that LD50 of the L. shawii extract was greater than 2000 mg/kg b.w in animal model [179]. |
| 45 | Solanum nigrum | Chlorogenic acid, quercetin, naringenin, solasodine, solamargine, solasonine, α-solanigrine, β-solanigrine, ascorbic acid, nigrumnins I and II [180] | S. nigrum extract at a dose of 2000 mg/kg p.o. was safe and showed no changes/alteration in normal behavior in animal model. No mortality was observed [181] |
| 46 | Withania somnifera | Withanolides, withaferin, withaferin A, withanone, withanolide A, withanolide IV, withanolide V, withanolide D [182]. | LD50value of W. somnifera extract in rates was greater than 2000 mg/kg body weight. Compared to the control group in subacute toxicity study, administration of extract did not show any toxicologically significant treatment-related changes in clinical observations, and the toxicological studies revealed that the reasonable doses of W. somnifera are nontoxic and safe [182, 183] |
| 47 | Lantana camara | Eicosane, squalene, β-ionone, caryophyllene oxide, β-caryophyllene, hexanoic acid, tiglic acid, lantanilic acid, camaric acid, lantadene B, oleanolic acid, lantadene A, lantaninilic acid, lantoic acid, ursolic acid, betulinic acid [184] | L. camara extracts at dose level of 2000 mg/kg and 5000 mg.kg body weight in mice and rats, respectively, showed no significant toxic signs or mortality [185, 186] |
| 48 | Peganum harmala | Harmine, harmaline, harmalol, harman, vasicine and vasicinone, pegamine, acacetin 7-O-rhamnoside, 7-O-6″-O-glucosyl-2 ″-O-(3‴-acetylrhamnosyl) glucoside, 7-0-(2‴-0-rhamnosyl-2″-O-glucosylglucoside), peganone 1 and 2, p-cymene, limonene, eugenol, thujico acid, β-cubebene [187–189] | P. harmala different doses of different extracts in animal and human clinical studies confirmed that this plant showed side effect like intoxications, abdominal writhing, body tremors, and toxic at high does level causing paralysis, liver degeneration, euphoria, convulsions, nausea, vomiting, hypothermia. However, therapeutic doses have been reported to be safe in a rodent model [189] |
| 49 | Tribulus terrestris | Naringin, rutin, hyperoside, quercitrin, naringenin, quercetin, hesperetin, kaempferol, apigenin, pyrogallol, gallic acid, catechin, catechol, chlorogenic acid, caffeic acid, vanillic acid, ferulic acid, salicylic acid, ellagic acid, coumaric acid, cinnamic acid [190] | T. terrestris extract showed no mortality/or toxicity at a dose up to 1 g kg−1 of bw in mice [190] |
| 50 | Urtica dioica | β-Amyrin, β-sitosterol, stigmasterol, oleanolic acid, ursolic acid, quercetin, rutin, chlorogenic, and 2-O-caffeoyl malic acid expressed as caffeic acid, isoquercetin, kaempferol 3-O-rutinoside [191–193]. | U. dioica extracts up to dose level of 2000 mg/kg body weight in animal model showed no mortality or changes/alteration in normal behavior [127]. |