A review on phytochemical, pharmacological and ethnopharmacological aspects of genus Trichodesma

Indian Journal of Natural Products and Resources Vol. 12(3), September 2021, pp. 333-347 A review on phytochemical, pharmacological and ethnopharmacological aspects of genus Trichodesma Ahmed A M Abdelgawad1,2*, Taha AI El-Bassossy1* and Fatma A Ahmed1 1 Medicinal and Aromatic Plants Department, Desert Research Center, Cairo, Egypt 2 Chemistry Department, Faculty of Science, Jazan University, Saudi Arabia Received 14 September 2020; Revised 18 April 2021 The genus Trichodesma belongs to the family Boraginaceae. The plants of this genus are widely distributed in tropical and subtropical regions of Africa, Asia, and Australia. Phytochemically, scientific reports on Trichodesma species so far revealed more than one hundred compounds from this genus, including hydrocarbons, phenols, flavonoids, sterols, terpenes and alkaloids have been isolated or identified. Medicinally, various reported biological activities of Trichodesma such as antimicrobial, antiparasitic, cytotoxic, anti-infection, antioxidant, anti-inflammatory, anti-irritant, antidiarrheal, antispasmodic, antimalarial, analgesic, antipyretic, anti-diabetic, diuretic, and hepatoprotective effects were discussed in this review otherwise. Also, the ethnopharmacological effects of this genus were reviewed. Among all the Trichodesma species, T. indicum is regarded as the most important one regarding its pharmacological values. The volatile oil of T. africanum L. showed high antioxidant activity. Keywords: Pharmacological properties, Phytoconstituents, Traditional uses, Trichodesma genus. IPC code; Int. cl. (2015.01)-A61K 36/00, A61K 36/30 Introduction Trichodesma R.Br. is a genus of about 45 species known from tropical and subtropical regions of Africa, Asia, and Australia1-4. Brown described Trichodesma in 18105. It belongs to the family Boraginaceae established by Jussieu6. The group comprises predominantly perennial herbs, a genus well defined by flowers with a deeply divided and strongly accrescent calyx, the absence of fomices, anthers usually with fairly long, soft hairs on the back and conspicuous long, linear, often twisted connectives produced above the thecae5. The name Trichodesma is derived from the Greek words, thrix or trikhos (hair), and desme (band or bundle) and alludes to the twisted hairs or awns that terminate the anthers. The species name is a reference to the relatively narrow leaves5. Morphologically, Trichodesma is characterized by the calathiform to broadly infundibular corolla with a short tube, naked throat and patent to reflexed lobes cuspidate at the apex. The stamens, typically exserted, have anthers usually pubescent outside that form a cone by long, aristate and spirally twisted appendages of the connective tissue7. —————— *Correspondent author Email:ahmedawad26@hotmail.com, tahachemist2008@gmail.com Pyrrolizidine alkaloids and triterpenoids are common secondary metabolites in Boraginaceae family and are widely isolated from several Trichodesma species8-11. Pharmacologically and phytochemically, only a few numbers of Trichodesma species have been reported including T. indicum (L.) R. Br., T. zeylanicum (Burm.f.) R. Br., T. incanum D. C., T. ehrenbergii Schweinf. ex Boiss., T. amplexicaule Roth., T. sedgwickianum Bane and T.africanum L. Among all the Trichodesma species, T. indicum (L.) R. Br. is regarded as the most important one considering its pharmacological values according to literature11-14. Further studies are needed to investigate pharmacological and phytochemical aspects of the other species belonging to this genus. So, in continuation of the authors’ research15-17, the present review aims to provide a point of reference for researchers to carry out more studies about Trichodesma plants. Methodology The authors searched databases of PubMed, Scopus, ProQuest, IEEE Xplore, EBSCO, ACS Publications, and Taylor & Francis etc. to find the relevant pharmacological properties of Trichodesma species as well as the literature dealing with the active constituents and ecological aspects. Keywords used for this research were “Trichodesma”, “pharmacology”, “ecology”, and 334 INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 “phytochemistry”. Data gathering from the mentioned databases was performed up to 31st November 2019 through the Egyptian Knowledge Bank (EKB) and Saudi Digital Library (SDL). Ethnopharmacological aspects Many Trichodesma plants have been used in traditional medicines throughout the world to treat common diseases, such as ear pain, intestinal worms, wounds, cough, fever, dysentery, and rheumatism. Available data about traditional uses of various species of Trichodesma, their local names, and plant parts used to treat human ailments by local practitioners are listed in Table 114,18-32. Phytochemical constituents Qualitative and quantitative analysis of Trichodesma species revealed the presence of many secondary metabolite's classes including alkaloids, steroids, flavonoids, phenolic acids, fatty acids, and hydrocarbons31,33-38. The categorization, structures, and sources of these compounds are listed in Tables 2-4. Aminoacids Amino acids are organic compounds that contain amine and carboxyl groups attached to the alphacarbon atom, along with a side chain specific to each amino acid39. Amino acids are the structural units (monomers) that makeup proteins. Because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, feed, and food technology. So far, twenty-two amino acids as free and protein amino acids with different ranges of concentrations were determined from T. ehrenbergii Schweinf. ex Boiss., T. indicum (L.) R. Br., and T. Zeylanicum (Burm.f.) R.Br as listed in Table 340-42. Cysteine is the common amino acid in the Trichodesma species. Essential oil constituents Essential oils are complex mixtures of volatile constituents frequently containing 20-60 or more individual compounds43. Common classes of compounds found in essential oils include hydrocarbons, esters, oxides, lactones, alcohols, phenols, aldehydes and ketones. These components have been reported to be responsible for several bioactivities ascribed to essential oils44. Essential oils have been recognized as therapeutic agents and widely utilized as potent natural medicinal components of plants45. Volatile oil from the leaves of T. africanum L. collected from Palestine was extracted using microwave, ultrasonic, microwave-ultrasonic, and conventional hydrodistillation methods. Among the four extraction methods used, the microwaveultrasonic method yielded the largest amount (1.8% v/w)34. Table 1 — Uses of Trichodesma species in folk medicines. Species T. indicum (L.) R. Br. T. zeylanicum (Burm.f.) R.Br. Country India India India India Part used LP RP LRP WP Pakistan Australia Tanzania Nigeria South Africa, Zimbabwe, and Comoros India India South Africa India India India Taiwan WP LP LP LP LP LP LRP Tubers WP RP WP LP Ailments treated Ear pain and wounds Dysentery, cough, cold, fever, anasarca and joint pain Tumour, snake-bite and urinary diseases Arthritis, anorexia, dysentery, skin diseases, snake-bite, fever, as emollient and as a diuretic. Intestinal worms As emollient and as diuretic Scalp fungal infection Fever, scorpion bite and as analgesic Wound healing, as analgesic, stillbirth, cough and scabies Wound healing Dysentery and rheumatism T. physaloides (Fenzl) A. DC. Treat schistosomiasis T. amplexicaule Roth. As emollient and poultice Reduce swellings and dysentry T. africanum L. As mollient andiuretic T. khasianum C. B.Clarke Ulcers, antihypertensive, promote digestion and improve flatulence T. sedgwickianum Bane India WP Emollient and poultice RP Reduce swelling of joints and depurative AP: Aerial parts; SP: Plant stems; WP: Whole plant; LP: Plant leaves; RP: Plant roots; LRP: Leaves and roots parts Ref. 18 19-22 14 19, 23 24 25 25 26 25 27-28 18 29-30 11 11 11 31 32 32 ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA 335 Table 2 — Preliminary phytochemical screening of the Trichodesma species Alkaloid + NA Phenolic ± + Flavonoid ± + T. africanum L. T. zeylanicum (Burm.f.) R.Br. T. sedgwickianum + + NA Bane T. ehrenbergii + + + Schweinf. ex Boiss. T. indicum (L.) R. NA + Br. T. khasianum NA + + C.B.Clarke NA = Not available; + = Present; − = Absent; ± = Weak Terpenoid + NA Tannin + + Saponin + + Anthraquinones − NA Volatile oil + NA Ref 33 34 + NA + NA NA 35 + + + NA − 36 + + + NA NA NA NA NA NA NA 37, 38 31 Table 3 — Free and protein amino acids identified from the Trichodesma species. Amino acid Aspartic acid Threonine Serine Glutamic acid Proline Hydroxy proline Glycine Alanine Cysteine Valine Methionine Isoleucine Leucine Tyrosine Phenyl alanine Lysine Histidine Arginine Cystine Amino n-butyric acid Ornithine Tryptophan References + = Present; - = Absent T. ehrenbergii Schweinf. ex Boiss. + + + + + + + + + + + + + + + + + 37 T.indicum (L.) R. Br. + + + + + + + + + 41-42 T. zeylanicum (Burm.f.) R.Br. + + + + + 41 Fatty acids and hydrocarbons Phenolics and flavonoids A fatty acid is a carboxylic acid consisting of a hydrocarbon chain and a terminal carboxyl group, especially any of those occurring as esters in fats and oils. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 2846. Phospholipids and triglycerides are the main precursors of fatty acids47. Twenty fatty acids, ester, and hydrocarbons identified from Trichodesma genus are summarized in Table 448-55. The structure of identified fatty acids and hydrocarbons is shown in Fig. 1. Phenolic compounds are a group of small molecules characterized by their structures having at least one phenol unit. Based on their chemical structures, phenolic compounds can be divided into different subgroups, such as phenolic acids, flavonoids, tannins, coumarins, lignans, quinones, and curcuminoids56. Phenolic compounds and flavonoids are widely distributed in nature and are the most abundant antioxidants in the diet, being the common components of fruits, vegetables, and their derivatives57-58. So far twenty-seven phenolics and flavonoids have been reported in various INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 336 Table 4 — Chemical constituents identified from Trichodesma species. Compound n-Decanyl laurate n-Tetradecanyl laurate n-Nonacosanyl palmitate n-Pentacos-9-one n-Dotriacont-9-one-13-ene Hexacosane Ethyl hexacosanoate 21, 24-Hexacosadienoic acid Oleic acid Linoleic acid Palmitic acid Stearic acid Linolenic acid Lauric acid Malvalic acid Hexacosanoic acid Ceryl alcohol Ricinoleic acid Myristic acid Sterculic acid Phenolic acids and flavonoids Ferulic acid Gallic acid Ellgaic acid Rosmarinic acid Protocatechuic acid Gentisic acid Chlorogenic acid Caffeic acid Syringic acid p-Coumaric acid Salicylic acid Quercitrin Naringenin Rutin Astralgalin Cynaroside Epicatechin Species Fatty acids and hydrocarbons T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. amplexicaule Roth. T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. indicum (L.) R. Br. T. zeylanicum (Burm.f.) R.Br. T. indicum (L.) R. Br. T. zeylanicum (Burm.f.) R.Br. T. indicum (L.) R. Br. T. zeylanicum (Burm.f.) R.Br. T. indicum (L.) R. Br. T. zeylanicum (Burm.f.) R.Br. T. indicum (L.) R. Br. T. zeylanicum (Burm.f.) R.Br. T. calcarata Batt. T. zeylanicum (Burm.f.) R.Br. T. zeylanicum (Burm.f.) R.Br. T. amplexicaule Roth. T. amplexicaule Roth. T. zeylanicum (Burm.f.) R.Br. T. zeylanicum (Burm.f.) R.Br. T. zeylanicum (Burm.f.) R.Br. T. ehrenbergii Schweinf. ex Boiss. T. khasianum C.B.Clarke T. ehrenbergii Schweinf. ex Boiss. T. indicum (L.) R. Br. T. sedgwickianum Bane T. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck T. khasianum C.B.Clarke T. ehrenbergii Schweinf. ex Boiss. T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. ehrenbergii Schweinf. ex Boiss. T. khasianum C.B.Clarke T. khasianum C.B.Clarke T. ehrenbergii Schweinf. ex Boiss. T. ehrenbergii Schweinf. ex Boiss. T. ehrenbergii Schweinf. ex Boiss. T. khasianum C.B.Clarke References 48 48 48 48 48 49 50 51 51 51 52 53 52 53 52 53 52 53 54 55 52 52 50 50 52 52 52 37 31 37 59 36 60 31 37 31 31 31 31 31 31 31 31 37 31 31 37 37 37 31 (Contd.) ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA Table 4 — Chemical constituents identified from Trichodesma species. Species Catechin T. indicum (L.) R. Br. T. sedgwickianum Bane Quercetin T. ehrenbergii Schweinf. ex Boiss. T. khasianum C. B. Clarke T. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck Kaempferol T. ehrenbergii Schweinf. ex Boiss. Luteolin T. ehrenbergii Schweinf. ex Boiss. Luteolin 7-O-α-L rhamnosyl (1-6)β-DT. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck glucoside Luteolin-7-diglucoside T. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck Apigenin T. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck 6-Hydroxy-4'-methoxy aurone T. ehrenbergii Schweinf. ex Boiss. Umbelliferone T. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck Scopoletin T. africanum (L.) R. Br. Var. heterotrichum Bornm and Kneuck Terpenoid β-Amyrin T. africanum L. α-Amyrin T. amplexicaule Roth. T. indicum (L.) R. Br. β-Methyl oleanate T. africanum L. Steroid β-Sitosterol T. Indicum (L.) R. Br. T. Africanum L. T. Amplexicaule Roth. T. Indicum (L.) R. Br. T. Sedgwickianum Bane Stigmasterol T. Africanum L. Stigmast-5-en-3β-ol-23-one T. Indicum (L.) R. Br. Stigmast-5-en-3 β-ol-21(24)-olide T. Indicum (L.) R. Br. Lanast-5-en-3β-D-glucopyranosyl-21(24)T. Indicum (L.) R. Br. olide Lupeol T. amplexicaule Roth. T. indicum (L.) R. Br. Alkaloid Viridiflorine T. africanum L. Intermedine T. africanum L. Lycopsamine T. africanum L. Retronecine T. africanum L. T. incanum D. C. Trichodesmine T. incanum D. C. T. africanum L. Europine T. africanum L. T. indicum (L.) R. Br. T. indicum (L.) R. Br. Monocrotolin Supinine T. ehrenbergii Schweinf. ex Boiss. T. indicum (L.) R. Br. Senkirkine T. ehrenbergii Schweinf. ex Boiss. Incanine T. incanum D. C. Quinine T. incanum D. C. Heliotrine T. indicum (L.) R. Br. Echimidine T. indicum (L.) R. Br. Compound species of Trichodesma. The whole description of these compounds can be found in Table 431,36-37,59-61 and their structures are shown in Fig. 2. 337 References 61 36 37 31 60 37 37 60 60 60 37 60 60 64 50 51 64 61 64 50 51, 36 36 64 48 48 48, 68 50 69 77 77 77 77 78 78-79 80-81, 64 80-83 80-83 69, 84 85 83 85 79, 86 78 83 83 Terpenoids Terpenoids, the largest family of natural products with more than 40,000 structures, refer to a large class of 338 INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 Fig. 1 — Chemical structure of fatty acids and hydrocarbons identified from Trichodesma species. Fig. 2 — Chemical structure of phenolic, flavonoid and coumarin compounds isolated from Trichodesma species. ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA oxygen-containing terpene analogues that can be found in all classes of living things. Like terpenes, they are all derived from five-carbon isoprene units assembled and modified in different ways62. Terpenoids can be widely found in plants, which are responsible for the scents, flavours, and even colours in many plants63. So far three terpenoid compounds namely α-amyrin, β-amyrin, and β-methyl oleanate were isolated from T. africanum L., T. amplexicaule Roth. and T. indicum (L.) R. Br50-51,64. The structure of isolated terpenoids is shown in Fig. 3. Steroids A steroid is a biologically active organic compound with four rings (three six-member and one fivemember) arranged in a specific molecular configuration. Squalene is the biochemical precursor to the whole family of steroids. Among all the steroid biosynthesis, 339 steroid hormone biosynthesis is the most concerned65-67. Six steroids isolated from Trichodesma species are listed in Table 436,48,50-51,61,64,68-69 and their structure is shown in Fig. 4. Alkaloids An alkaloid has been defined by Pelletier as ''a cyclic organic compound containing nitrogen in a negative oxidation state which is of limited distribution among living organisms''70. Various amino acids molecules are often their precursors71. Alkaloids have a wide range of pharmacological activities including antimalarial, antiasthma, anticancer, cholinomimetic, vasodilatory, antiarrhythmic, analgesic, antibacterial, and antihyperglycemic activities72-76. Pyrrolizidine alkaloids have been common in subfamilies of the Boraginaceae family and are widely isolated from a few species of Fig. 3 — Chemical structure of terpenoid compounds isolated from Trichodesma species. Fig. 4 — Chemical structure of steroid compounds isolated from Trichodesma species. 340 INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 Trichodesma. Thirteen alkaloid compounds were isolated from Trichodesma species. The isolated alkaloids are listed in Table 464,69,77-86 and their structure is shown in Fig. 5. Pharmacological effect Pharmacology is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals87. Antimicrobial activity Antimicrobial activity refers to the process of killing or inhibiting the disease-causing microbes. Various antimicrobial agents are used for this purpose. Antimicrobial may be anti-bacterial, anti-fungal or antiviral. They all have different modes of action by which they act to suppress the infection. Antimicrobial activity of T. sedgwickianum Bane25,36, T. africanum (L.) R. Br. var. heterotrichum Bornm and Kneuck60, T. amplexicaule Roth.50, T. indicum (L.) R. Br.48,59,88,89, T. africanum L.90, and T. ehrenbergii Schweinf. ex Boiss.91 was investigated by various known methods like disk-diffusion, broth or agar dilution etc. The inhibition zone and the minimum inhibitory concentration (MIC) were determined for various concentrations of each plant extract. Almost all these species showed fair to high antimicrobial activity against various grampositive and gram-negative bacterial and fungal strains. Also, the volatile oil of T. africanum L. exhibited significant antimicrobial activities with MIC for Escherichia coli, Pseudomonas aeruginosa, Fig. 5 — Chemical structure of alkaloid compounds isolated from Trichodesma species. ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA Staphylococcus aureus, and Candida albicans were 3, 5, 6, 3, and 9, respectively34. Antiparasitic activity Antiparasitics are a class of medications that are indicated for the treatment of parasitic diseases, such as those caused by helminths92, amoeba93, ectoparasites, parasitic fungi94, and protozoa92, among others. Antiparasitics target the parasitic agents of the infections by destroying them or inhibiting their growth; they are usually effective against a limited number of parasites within a particular class. Antiparasitics are one of the antimicrobial drugs which include antibiotics that target bacteria, and anti-fungal that target fungi. They may be administered orally, intravenously or topically. In vitro bioassay screening of methanol extracts of T. africanum L. growing in Egypt, was carried out for schistosomicidal activity. The extract was bioassayed at 100 µg/mL on viable Schistosoma mansoni mature worms in a culture medium. The viability of worms was examined after exposure for 24 h, and mortality was determined. T. africanum L. was found to possess weak reproducible in an in vitro antischistosomal activity95. Cytotoxicity activity Cytotoxic agents are a substance used in the treatment of malignant and other diseases. They are designed to destroy rapidly growing cancer cells. They have been shown to be mutagenic, carcinogenic and/or teratogenic, either in treatment doses or animal and bacterial assays96. The cytotoxic activity of Trichodesma species was studied by one of the most well-known techniques 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or lactate dehydrogenase (LDH) and the half-maximal inhibitory concentration (IC50) was calculated. T. africanum L. and T. trichodesmoides var. tomentosum R. Mill. showed no cytotoxic activity against MRC-5 (IC50> 64)97, also, T. ehrenbergii Schweinf. ex Boiss. showed weak cytotoxicity against liver carcinoma cell line (HEPG-2) and lung carcinoma cell (A-549) with IC50 38.4 and 55.6 μg/mL, respectively37, furthermore, the hydroalcoholic extract of the whole plant of T. indicum (L.) R. Br. exhibited poor cytotoxic properties against L6 Cell Line98. On the other hand, T. africanum L. aerial parts, given at different dose levels (300, 75 mg/kg/day) indicated that the plant extracts are toxic and lethal to Wistar rats by whatever route (oral or intramuscular) it was given64,99. Generally, Tricodesma showed no cytotoxic activity. 341 Anti-infection activity Infections caused by protozoa such as Trypanosoma, Plasmodium, and Leishmania are a major worldwide health problem causing significant morbidity and mortality in Africa, Asia, and Latin America. Malaria kills between one and two million people annually, the majority of those affected being children under the age of five and pregnant women100. T. Africanum L. and T. trichodesmoides var. tomentosum R. Mill. showed non-significant as antimalarial, antitrypanosomal against Trypanosoma brucei (IC50 32 and >64) and Trypanosoma cruzi (IC50> 64 and 29), and Antiplasmodial against Plasmodium falciparum (IC50 32 and 25), respectively97. Also, T. africana, T. africanum L., and T. trichodesmoides var. tomentosum R. Mill. were non-significant as antileishmanial against Leishmania infantum97 and Leishmania major101 with IC50 between 43-64. The reported Tricodesma species were non-significant as antimalarial, antitrypanosomal, antiplasmodial and antileishmanial. Antioxidant activity Most foods are made up of several organic compounds that can easily undergo oxidation. Lipids (such as fats, oils, and waxes) in general have the greatest tendency to lose electrons. Antioxidants were used to prevent the oxidation process in foods which lead to rancidity and browning, DNA oxidation and have many positive physiological effects in human102. Various antioxidants are supplied to the human body through diet, both vegetarian as well as non-vegetarian. Vitamins C and E, β-carotene and coenzyme Q are the most common antioxidants of diet103-105. The most promising methods used to evaluate antioxidant properties are DPPH (2,2-Diphenyl-1-picrylhydrazyl) scavenging method106 and ABTS (2,2'-azino-bis(3ethylbenzothiazoline-6-sulfonic acid)). Antioxidant activity of many Trichodesma species (T. sedgwickianum Bane36, T. trichodesmoides Gürke107, T. indicum (L.) R. Br. 61,98,108, T. khasianum C. B. Clarke31, T. zeylanicum (Burm.f.) R.Br.35, T. amplexicaule Roth.109 from different countries was assayed by free radical scavenging by ABTS, DPPH, and nitric oxide and superoxide radical methods. The volatile oil of T. africanum L. exhibited antioxidant activity in terms of inhibition (91.83%±1.1)34. So far, Trichodesma species have revealed weak to good antioxidant effect. Anti-inflammatory activity Inflammation is a typical reaction by vascular tissues in biological systems against dangerous 342 INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 external stimuli, such as an attack of a pathogen, irritants that lead to local accumulation of plasma, blood cells, and damaged cells. It is the resistance offered by the organism against any external factor causing damage, and it then heals any injury that occurred in any tissue71. It has been reported that a T. indicum (L.) R. Br. root extract has anti-inflammatory activity against histamine and serotonin-induced oedema in rats48. In addition, T. amplexicaule Roth. showed dramatic anti-inflammatory effects in the suppression of carrageenan-induced acute arthritis and complete Freund's adjuvant (CFA)-induced chronic arthritis in rats110. Moreover, T. khasianum C. B. Clarke dramatically decreased the protein levels of proinflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NO (nitric oxide), and prostaglandin E2 (PGE2) in a dosedependent manner in lipopolysaccharide (LPS)treated RAW264.7 macrophages31. Trichodesma had a dramatically anti-inflammatory effect. Anti-irritant/anti-sting activity Anti-irritants, whether naturally occurring or manmade, are substances that provide a soothing effect to irritated skin and reduce damage by a variety of mechanisms, including reduced absorption and/or biochemical manipulation of noxious chemicals111. Topical application revealed that T. lanicum seed extract reduces or eliminates the irritation or sting induced by the topical application of hydroxy acids (HAS) and/or retinoids. T. lanicum seed extract is claimed as an anti-irritant/anti-sting agent due to it contains cosmetic compounds likes hydroxy acids and/or retinoids and further compounds112-113. Antidiarrheal activity Antidiarrheals are the name given to certain types of medicines that stop or slow diarrhoea. Antidiarrheals only relieve the symptoms of diarrhoea, such as an increased frequency and urgency when passing stools, they do not eliminate the cause of it. The ethanolic extract of T. indicum (L.) R. Br. roots significantly inhibited the castor oil-induced diarrhoea in rats and decrease the propulsion of charcoal meal through the gastrointestinal tract. It also reduced the castor oil-induced small intestinal fluid accumulation. The root of T. indicum (L.) R. Br. has significant antidiarrheal activity and proves the use of this herbal remedy as nonspecific treatment of diarrhoea in folk medicine114. Antispasmodic activity Antispasmodic compounds are currently used to reduce anxiety, emotional, and musculoskeletal tension, and irritability. Although most of the available antispasmodic compounds are synthetic or semisynthetic, traditional uses of this group of compounds are still popular115. The water extract of the leaves of T. africana from the United Arab Emirates (UAE) showed an inhibitory action on the spontaneous contractions of rabbit jejunal tissue, indicating antispasmodic activity with an IC50 12.53 mg/mL and the percentage of maximum inhibition Imax was 61(Ref. 116). Antidiabetic activity Diabetes is a group of metabolic disorders characterized by a high blood sugar level over a prolonged time. Symptoms often include frequent urination, increased thirst, and increased appetite. If left untreated, diabetes can cause many complications. Antidiabetic agents aim to reduce blood sugar levels to an acceptable range and relieve symptoms of diabetes such as thirst, excessive urination, and ketoacidosis. Antidiabetic agents also prevent the development of or slow the progression of, long-term complications of the disease, such as nephropathy, neuropathy, and retinopathy. Antidiabetic effect of the hydroalcoholic extract of the whole plant of T. indicum (L.) R. Br. was studied using the glucose uptake model in rodent skeletal muscle cells (L-6 cells) involved in glucose utilization. T. indicum (L.) R. Br. extract exhibited moderate antidiabetic activity98. Also, the methanolic extract of the plant leaves showed moderate α-amylase inhibitory activity (IC50= 91.3 μg/mL). Almost all the tested extracts prominently reduce blood glucose levels in streptozotocin (STZ)-nicotinamide induced Type 2 diabetic rats. The methanolic extract has shown an estimable decrease of blood glucose level (P <0.01) along with glibenclamide. The results confirmed the anti-diabetic property of the plant extract against Type 2 diabetes mellitus117. Diuretic activity Diuretic compounds that stimulate the excretion of water are potentially useful in most disorders including those exhibiting oedemata such as congestive heart failure, nephritis, toxemia of pregnancy, premenstrual tension and hypertension. Some of the diuretics are derived from medicinal plants118. Methanol and aqueous extracts of aerial parts of T. indicum (L.) R. Br. (150 and 300 mg/kg) were used ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA for screening diuretic activity using the Lipschitz model. The urine volume of the methanolic extract at a dose of 300 mg/kg has significant diuretic activity (P ≤0.001) with Lipschitz value 1.25 as compared to standard (Furosemide). Urinary sodium concentration was found to be more in methanol extract, but potassium was found to be more in aqueous extract. It also shows methanol extract has an effect like K+ sparing diuretics119. Hepatoprotective activity The liver performs the normal metabolic homeostasis of the body as well as biotransformation, detoxification and excretion of many endogenous and exogenous compounds, including pharmaceutical and environmental chemicals. Drug-induced hepatotoxicity is a major cause of iatrogenic diseases, accounting for one in 600 to one in 3500 of all hospital admissions. There is a lack of reliable hepatoprotective drugs in modern medicine to prevent and treat drug-induced liver damage120. T. sedgwickianum Bane and T. ehrenbergii Schweinf. ex Boiss. demonstrated hepatoprotective activity by reducing the carbon tetrachloride-induced elevated level of various liver enzymes. These plants revealed potent hepatoprotective activity against the toxic effect of carbon tetrachloride comparable to the silymarin treated group36-37. Analgesic and antipyretic activity Analgesic and antipyretic activities are commonly mentioned as characteristics of drugs that have an inhibitory effect on prostaglandin biosynthesis. The possible analgesic and antipyretic potential of the plant were studied using several experimental models. The analgesic activity was determined in chemicals (acetic acid and formalin) as well as thermal (tail immersion) pain models in mice using classical standard drugs. The ethanol extract at doses of 100, 200, and 400 mg/kg exhibited a significant (P <0.001) inhibition of acetic acid-induced abdominal constrictions in the mouse. In the tail immersion models, the extract (400 mg/kg) showed a significant increase (P <0.001) in pain threshold to the meal stimulus and also in both the phase (early and late phase) of the hyper analgesic mode of formalin test121. The ethanolic extract of 400 mg/kg significantly inhibited both phases of the hyperalgesic mode of the formalin test and produced less effect in the first and more in the second phase. A rectal temperature was reduced up to 3 hours after administration in rats. The 343 extract also reduced the rectal temperature in rats in yeast induced pyrexia for up to 4 hours after the administration and the efficacy produced was similar to that of standard drug. The results suggested that the extracts of different dose levels showed analgesic and antipyretic activity121. Conclusion Plants of the genus Trichodesma have many bioactive constituents, many of which have been used in traditional folk medicine throughout the world. Phytochemical investigations of various Trichodesma species have revealed that many components from this genus express significant biological and pharmacological activities. Nevertheless, there are still many Trichodesma species that have received very little or no attention. Further phytochemical and biological studies should be done on these plants. So, this review is an attempt to document the information on different aspects of Trichodesma bioactivity and highlight the need for further research and development. Conflict of interest The authors have declared that there is no conflict of interest. References 1 2 3 4 5 6 7 8 9 10 11 12 Boulos L, Flora of Egypt, (Al-Hadara Publishing, Cairo), 2000, 286-287. Brand A, Borraginaceae-Borraginoideae-Cynoglosseae, In Das Pflanzenreich., edited by A Engler (Leipzig: Verlag von Wilhelm Engelmann), 1921, 19-44. Verdcourt B, Boraginaceae, in Flora of Tropical East Africa, edited by B A Polhill (CRC Press, Florida), 1991, 1-124. Mabberley D J, The plant-book, 2nd edn, (Cambridge University Press, Cambridge), 1997. Retief E, The genus Trichodesma (Boraginaceae: Boraginoideae), in Southern Africa, Bothalia, 2002, 32, 151-166. Jussieu A L, Genera plantarum, (Herissant & Barrois, Paris), 1789. Mosti S and Selvi F, Trichodesma cinereum (Boraginaceae), a new species from Oman, Candollea, 2007, 62(2), 205-210. Nadkarni A K and Nadkarni K M, Indian Materia Medica, (Popular Book Depot, Bombay), 1954. Manske R H F, The Alkaloids, (Academic Press, London), 1970. Anonymous, The Wealth of India, (CSIR, New Delhi), 1976. Sharma R A, Singh B and Singh D, Ethnomedicinal, pharmacological properties and chemistry of some medicinal plants of Boraginaceae in India, J Med Plants Res, 2009, 3(13), 1153-1175. Hem K, Sharma V, Kumar D, Singh N K and Gautam D N S, Ethanopharmacology, pharmacology and Phytochemistry of Trichodesma indicum (Linn.) R. Br., Indian J Agric Sci, 2015, 1(4), 141-150. 344 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 Hamsalakshmi, Joghee S, Babu S and Silpa M, Trichodesma indicum – an Overview, Int J Pharm Sci Rev Res, 2018, 48(2), 63-69. Mangai S A, Pharmacological efficacy of Trichodesma indicum (Linn) R. Br., in folk medicine – an updated review, Asian J Pharm Clin Res, 2018, 11(3), 24-27. Atta E M, Hegab K H, Abdelgawad A A M and Youssef A A, Synthesis, characterization and cytotoxic activity of naturally isolated naringin metal complexes, Saudi Pharm J, 2019, 27, 584-592. El-Desouky S K, Abdelgawad A A, El-Hagrassi A M, Hawas U W and Kime Y K, Chemical composition, cytotoxic and antioxidant activities of Celosia trigyna L. grown in Saudi Arabia, Acta Pol Pharm, 2019, 76(4), 691-699. Abd El Azim M H M, El-Mesallamy A M D, El-Gerby M and Awad A, Anti-Tumor, antioxidant and antimicrobial and the phenolic constituents of clove flower buds (Syzygium aromaticum), J Microb Biochem Technol, 2014, S8:007, 1-4. Ignacimuthu S, Ayyanar M, and Sankarasivaraman K, Ethnobotanical study of medicinal plants used by Paliyar tribals in Theni district of Tamil Nadu, India, Fitoterapia, 2008, 79(7-8), 562–568. Sankaranarayanan S, Bama P, Ramachandran J, Kalaichelvan P T, Deccaraman M, et al., Ethnobotanical study of medicinal plants used by traditional users in Villupuram district of Tamil Nadu, India, J Med Plants Res, 2010, 4(12), 1089-1101. Chopra R N, Chopra I C, Handa K L and Kapur L D, Indigenous Drugs of India, (U.N Dhur and Sons Pvt. Ltd, Calcutta), 1958, 528. Agarwal V S, Drug Plants of India, (Kalyani Publishers, New Delhi), 1997, 694. Srikanth K, Murugesan T, Kumar C A, Suba V, Das A K, et al., Effect of Trichodesmaindicum extract on cough reflex induced by sulphur dioxide in mice, Phytomedicine, 2002, 9(1), 75-77. Parrotta A J, Healing Plants of Peninsular India, (CABI Publishing, New York), 2001, 185. Abbasi A M, Khan M A, Ahmed M and Zafar M, Herbal medicines used to cure various ailments by the inhabitants of Abbottabad district, North West Frontier Province, Pakistan, Indian J Tradit Know, 2010, 9(1), 175-183. Maregesi S M, Nyamwisenda N T, Mwangomo D and Kidukuli A, In vitro antimicrobial activity and determination of essential metal and ash value contents of Trichodesma zeylanicum, Int J Res Pharmacol Pharmacerapeutic, 2013, 2, 417-424. Iwu M M, Handbook of African medicinal plants, (CRC press Boca Raton, Florida), 1993. Ayyanar M and Ignacimuthu S, Herbal medicines for wound healing among tribal people in Southern India: Ethnobotanical and scientific evidences, Int J Appl Res Nat Prod, 2009, 2(3), 29-42. Ngonda F, Evaluation of the wound healing potential of Trichodesma zeylanicum (Burm. f.) formulation in excision wounds in albino rats, Annu Res Rev Biol, 2014, 4(6), 828-839. Gelfand M, Mavi S, Drummond R B, Ndemera B, The traditional medicinal practitioner in Zimbabwe: his principles of practice and pharmacopeoia, (Mambo Press, Gweru), 1985. 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 Sparg S G, van Staden J, Jäger A K, Efficiency of traditionally used South African plants against schistosomiasis, J Ethnopharmacol, 2000, 73(1-2), 209-214. Chen S-Y, Wang G-Y, Lin J-H and Yen G-C, Antioxidant and anti-inflammatory activities and bioactive compounds of the leaves of Trichodesma khasianum Clarke, Ind Crops Prod, 2020, 151, 112447. Saboo S S, Tapadiya G G and Khadabadi S S, Development of pharmacognostic standards of plants from Borginaceae family, Asian Pac J Trop Biomed, 2012, 2(2), S589-S592. Al-Tameme H J, Hadi M Y and Hameed I H, Phytochemical analysis of urtica dioica leaves by fourier-transform infrared spectroscopy and gas chromatography-mass spectrometry, J Pharmacogn Phytother, 2015, 7(10), 238-252. Jaradat N, Zaid A, Abuzant A and Shawahna R, Investigation the efficiency of various methods of volatile oil extraction from Trichodesma africanum and their impact on the antioxidant and anti-microbial activities, J Intercult Ethnopharmacol, 2016, 5(3), 250. Ngonda F, In-vitro antioxidant activity and free radical scavenging potential of roots of Malawian Trichodesma zeylanicum, Asian J Biomed Pharm Sci, 2013, 3(20), 21-25. Saboo S S, Tapadiya G, Farooqui I A and Khadabadi S S, Free radical scavenging, in vivo antioxidant and hepatoprotective activity of folk medicine Trichodesma sedgwickianum, Bangladesh J Pharmacol, 2013, 8(1), 58-64. Ahmed F A, El-Mesallamy A M D and El-Bassossy T A I, Hepatoprotective and antitumor activity of phenolic content of trichodesma ehrenbergii schewienf. Ex boiss. Aerial parts, World J Pharm Med Res, 2016, 2(4), 119-125. Manani L M, Saluja A K and Prajapati P R, Pharmacognostical and preliminary phytochemical investigations of aerial parts of Trichodesma indicum R .Br., Int J Pharm Pharm Sci, 2015, 7(11), 157-162. Nelson D L and Cox M M, Principles of Biochemistry, 4th edn, (W. H. Freeman & Co., New York), 2005. Narayana L L and Satyavathi D V L, The distribution pattern of free amino acids in certain Boraginaceae, Feddes Repert, 1990, 101(11-12), 593-599. Mondal A K, Mondal S and Mandal S, The free amino acids of pollen of some angiospermic taxa as taxonomic markers for phylogenetic interrelationships, Curr Sci, 2009, 96(8), 1071-081. Shankar K R, Gurjar C, Rajalakshmi V G and Joshi N H, Phytochemical Investigations of Plant Trichodesma Indicum, Biomed Pharmacol J, 2008, 1(2), 453-456. Miguel M G, Antioxidant and anti-inflammatory activities of essential oils: A short review, Molecules, 2010, 15(12), 9252-9287. de Sousa D P, Júnior G A, Andrade L N and Batista J S, Spasmolytic activity of chiral monoterpene esters, Rec Nat Prod, 2011, 5(2), 117-122. Djilani A and Dicko A, The therapeutic benefits of essential oils, in Nutrition, well-being and health, edited by J Bouayed and T Bohn, (IntechOpen, London), 2012, 155-179. Moss G P, Smith P A S and Tavernier D, Glossary of class names of organic compounds and reactivity intermediates based on structure (IUPAC Recommendations 1995), Pure Appl Chem, 1995, 67(8-9), 1307-1375. Ibrahim M, Rehman K, Hussain I, Farooq T A, Ali B, et al., ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Ethnopharmacological investigations of phytochemical constituents isolated from genus Cuscuta, Crit Rev Eukaryot Gene Expr, 2017, 27(2), 113-150. Perianayagam J B, Sharma S K and Pillai K K, Anti-inflammatory activity of Trichodesma indicum root extract in experimental animals, J Ethnopharmacol, 2006, 104(3), 410-414. Kirtikar K R and Basu B D, Indian Medicinal Plants, (Srisatguru Publications, Delhi), 2000, 2335-2337. Singh B and Singh S, Antimicrobial activity of terpenoids from Trichodesma amplexicaule Roth., Phytother Res, 2003, 17(7), 814-816. Ahmad S, Hasan M and Mohamood K, Chemical investigation of Trichodesma indicum leaves-I. non-steroidal constituents of the petroleum ether Extract, J Chem Society Pak, 1982, 4, 281-283. Hosamani K M, Ricinoleic and cyclopropene acids in Trichodesma zeylanicum seed oil, Phytochem, 1994, 37(6), 1621-1624. Badami R C, Deshpande G S and Shanbhag M R, Minorseedoils. VII. Examination of seed oils by gas-liquid chromatography, J Oil Technol Assoc India, 1975, 7, 76–77. Rao K S and Sino D, Fatty acid composition of 20 lesserknown Western Australian seed oils, J Sci Food Agric, 1992, 58(4), 585-587. Guil-Guerrero J L, López-Martínez J C, Gómez-Mercado F and Campra-Madrid P, Gamma-linolenic and stearidonic acids from Moroccan Boraginaceae, Eur J Lipid Sci Technol, 2006, 108(1), 43-47. Gan R-Y, Chan C-L, Yang Q-Q, Li H-B, Zhang D, et al., Bioactive compounds and beneficial functions of sprouted grains, in Sprouted Grains, edited by H Feng, B Nemzer and J W DeVries (AACC International Press), 2019, 191-246. Ruiz-Ruiz J C, Aldana G D C E, Cruz A I C and SeguraCampos M R, Antioxidant activity of polyphenols extracted from hop used in craft beer, in Biotechnological Progress and Beverage Consumption, vol 19: The Science of Beverages, edited by A M Grumezescu and A M Holban, (Academic Press, New York), 2020, 283-310. Abdelgawad A A, Tamarix nilotica (Ehrenb) Bunge: A review of phytochemistry and pharmacology, J Microb Biochem Technol, 2017, 9(1), 544-553. Saboo S S, Tapadiya G G and Khadabadi S S, Antimicrobial potential of tropical plant Trichodesma indicum (L.) R. Br. and Trichodesma sedgwickianum, Res J Microbiol, 2013, 8(1), 63-69. El-Moaty H I A, Active constituents and antimicrobial activity of Trichodesma africanum L. (L.) R.Br. var. heterotrichum Bornm. & Kneuck, Bull Fac Agric, Univ Cairo, 2009, 60(4), 357-365. Hariram S K, Anusha K, Balakrishnan S and Sindhu S, Screening the metal chelating efficacy of Trichodesma indicum, Res J Pharm Biol Chem Sci, 2014, 5(2), 1259-1262. Roberts S C, Production and engineering of terpenoids in plant cell culture, Nat Chem Biol, 2007, 3(7), 387-395. Specter M, A life of its own: where will synthetic biology lead us?, New Yorker, 2009, 56-65. Omar M, De Feo J and Youngken H W, Chemical and toxicity studies of Trichodesma africanum L., J Nat Prod, 1983, 46(2), 153-156. 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 345 Tong W-Y, Zhang X-C, Jiang Q and Xiang D, Integrated biotechnology: Fundamentals and applications, 1st edn., (Studium Press LLC, Houston), 2012 Reinert D J, Balliano G and Schulz G E, Conversion of squalene to the pentacarbocyclic hopene, Chem Biol, 2004, 11(1), 121-126. Godio R P, Fouces R and Martin J F, A squalene epoxidase is involved in biosynthesis of both the antitumor compound clavaric acid and sterols in the basidiomycete H. sublateritium, Chem Biol, 2007, 14(12), 1334-1346. Mustafa Din W, A phytochemical and pharmacological study of acalypha wilkesiana var. macafeana hort. (euphorbiaceae juss.): antioxidant and antibacterial analyses, PhD thesis, University of Nottingham, Selangor, 2014. Pandi K P, Ayyanar M and Ignacimuthu S, Medicinal & poisonous plants of India, Ind J Trad Know, 2013, 6(4), 579-582. Verpoorte R, Alkaloids, in Encyclopedia of Analytical Science, 2nd edn, edited by P Worsfold, A Townshend and C Poole, (Elsevier), 2005, 56-61. Ibrahim M, Rehman K, Razzaq A, Hussain I, Farooq T, et al., Investigations of phytochemical constituents and their pharmacological properties isolated from the genus Urtica: critical review and analysis, Crit Rev Eukaryot Gene Expr, 2018, 28(1), 25-66. Kittakoop P, Mahidol C and Ruchirawat S, Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation, Curr Top Med Chem, 2014, 14(2), 239-252. Russo P, Frustaci A, Del Bufalo A, Fini M and Cesario A, Multitarget drugs of plants origin acting on Alzheimer's disease, Curr Med Chem, 2013, 20(13), 1686-1693. Sinatra R S, Jahr J S and Watkins-Pitchford J M, The Essence of Analgesia and Analgesics, (Cambridge University Press), 2010, 82-90. Cushnie T P, Cushnie B and Lamb A J, Alkaloids: An overview of their antibacterial, antibiotic-enhancing and antivirulence activities, Int J Antimicrob Agents, 2014, 44(5), 377-386. Qiu S, Sun H, Zhang A H, Xu H Y, Yan G L, et al., Natural alkaloids: Basic aspects, biological roles, and future perspectives, Chin J Nat Med, 2014, 12(6), 401-406. El-Shazly A, El-Domiaty M, Witte L and Wink M, Pyrrolizidine alkaloids in members of the Boraginaceae from Sinai (Egypt), Biochem Syst Ecol, 1998, 26(6), 619-636. Menschikow G and Rubinstein W, Über ein Alkaloid aus Trichodesma incanum D. C. (I. Mitteil.), Ber dtsch Chem Ges A/B, 1935, 68(11), 2039-2044. Copper R A, Bowers R J, Beckham C J and Uxtable R J, Preparative separation of pyrrolizidine alkaloids by highspeed counter-current chromatography, J Chromatogr A, 1996, 732(1), 43-50. Mattocks A R, Chemistry and Toxicology of Pyrrolizidine Alkaloids, (Academic Press, London), 1986. Hartmann T and Witte L, Chemistry, biology and chemoecology of pyrrolizidine alkaloids, In Alkaloids: Chemical and Biological Perspectives, vol. 9, edited by S W Pelletier, (Pergamon, Oxford), 1995, 155-233. Zalkow L H, Bonetti S, Gelbaum L, Gordon M M, Patil B B, et al., Pyrrolizidine alkaloids from middle eastern plants, J Nat Prod, 1979, 42(6), 603-614. 346 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 INDIAN J NAT PROD RESOUR, SEPTEMBER 2021 Ahmad L, He Y, Semotiuk A and Liu Q, Qualitative determination of toxic pyrrolizidine alkaloids in Trichodesma indicum: A prevalent ethnomedicine of Northern Pakistan, J Complementary Med Res, 2018, 9(2), 11-23. Saboo S S, Tapadiya G G, Lamale J J and Khadabadi S S, Phytochemical screening and antioxidant, antimitotic, and antiproliferative activities of Trichodesma indicum shoot, Anc Sci Life, 2014, 34(2), 113-118. Wassel G, El-Menshawi B, Saeed A and Mahran G, Toxic pyrrolizidine alkaloids of certain boraginaceous plants, Acta Pharm Suec, 1987, 24(4), 199-204. Sadykov Yu. D and Khodzhimatov, Alkaloids of Trichodesmaincanum DC., Doklady Akademii Nauk Tadzhikskoi SSR, 1979, 22(4), 249-252. Vallance P and Smart T G, The future of pharmacology, Br J Pharmacol, 2006, 147(Suppl 1), S304-S307. Chidambaram A R and Aruna A, Pharmacognostic study and development of quality parameters of whole plants of Trichodesma indicum (linn.) R.br., Asian J Pharm Clin Res, 2013, 6(3), 167-169. Sharanya M, Oviya I R, Poornima V and Jeyam M, Antifungal susceptibility testing of few medicinal plant extracts against Aspergillus spp. and Microsporum sp., J Appl Pharm Sci, 2013, 3(8 Suppl 1), S12-S16. Abdallah E M and El-Ghazali G E, Screening for antimicrobial activity of some plants from Saudi folk medicine, Global J Res Med Plants Indigen Med, 2013, 2(4), 210-218. El-Mesallamy A, Ahmed F A, Elhaw M H and Ibrahim T A, Chemical investigation and evaluation of antimicrobial activity of trichodesma ehrenbergii Schweinf. ex Boiss. schweinf. Ex boiss. growing widely in Gebel Elba, Egypt, Indo American J Pharm Sci, 2015, 2(5), 961-966. Kappagoda S, Singh U and Blackburn B G, Antiparasitic therapy, Mayo Clin Proc, 2011, 86(6), 561-583. Kusrini E, Hashim F, Azmi W N, Amin N M and Estuningtyas A, A novel antiamoebic agent against Acanthamoeba sp. - A causative agent for eye keratitis infection, Spectrochim Acta a Mol Biomol Spectrosc, 2016, 153, 714-721. Molina J-M, Tourneur M, Sarfati C, Chevret S, de Gouvello A, et al., Fumagillin treatment of intestinal microsporidiosis, N Engl J Med, 2002, 346(25), 1963-1969. Yousif F, Hifnawy M S, Soliman G, Boulos L, Labib T, et al., Large-scale in vitro screening of Egyptian native and cultivated plants for schistosomicidal activity, Pharm Biol, 2007, 45(6), 501-510. Willemson-McBride T L and Gehan K, Safe handling of cytotoxic agents: A team approach, AORN J, 2009, 90(5), 731-740. Abdel-Sattar E, Maes L and Salama M M, In vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease, Phytother Res, 2010, 24(9), 1322-1328. Sudharshan R D, Srinivasa R A and Ananth P H, In vitro antioxidant and glucose uptake effect of Trichodesma indicum in l-6 cell lines, Int J Pharm Bio Sci, 2012, 3(4), 810-819. Adam S I Y and Adam S E I, Comparative toxicity of Trichodesma africanum and Rhanteriumepapposum aerial parts aqueous and methanolic extracts on wistar rats, J Pharmacol Toxicol, 2012, 7(3), 128-139. 100 Snow W, Guerra C A, Noor A M, Myint H Y and Hay S I, The global distribution of clinical episodes of Plasmodium falciparum malaria, Nat, 2005, 434, 214-217. 101 Al Nasr I, In Vitro anti-leishmanial assessment of some medicinal plants collected from Al Qassim, Saudi Arabia, Acta Parasitologica, 2020, 65, 696-703. 102 Atta E M, Mohamed N H and Abdelgawad A A M, Antioxidants: An overview on the natural and synthetic types, Eur Chem Bull, 2017, 6, 365-375. 103 Vajragupta O, Boonchoong P and Berliner L J, Manganese complexes of curcumin analogues: Evaluation of hydroxyl radical scavenging ability, superoxide dismutase activity and stability towards hydrolysis, Free Radic Res, 2004, 38(3), 303-314. 104 Giles G I and Jacob C, Reactive sulfur species: An emerging concept in oxidative stress, Biol Chem, 2002, 383(3-4), 375-388. 105 El-Mesallamy A M D, El-Gerby M, Abdel Azim M H M and Awad A, Antioxidant, antimicrobial activities and volatile constituents of clove flower buds oil, J Essent Oil-Bear Plants, 2012, 15(6), 900-907. 106 Krishnaiah D, Sarbatly R and Nithyanandam R, A review of the antioxidant potential of medicinal plant species, Food Bioprod Process, 2011, 89(3), 217-233. 107 Abdallah H M, Abdel-Naim A B, Ashour O M, Shehata I A and Abdel-Sattar E A, Anti-inflammatory activity of selected plants from Saudi Arabia, Z Naturforsch C J Biosci, 2014, 69(1-2), 1-9. 108 Devi G S, Sangeetha S and Das M S, Comparative evaluation of phytochemicals and antioxidant potential of Cleome viscose and Trichodesma indicum, Int J Pharm Sci Rev Res, 23(1), 253-258. 109 Avanapu S R, Reddy D S and Ananth P H, Free radical scavenging effect of Trichodesma amplexicaule Roth. against renal vascular complications in diabetic Rats, Int J Phytomed, 2012, 4(4), 461-468. 110 Singh B, Sahu P M, Lohiya R K, Sharma M K, Singh H L, et al., Anti-inflammatory activity of alkanoids and triterpenoids from Trichodesma amplexicaule Roth., Phytomedicine, 2006, 13(3), 152-156. 111 Ford C and Maibach H I, Anti-irritants: Myth or reality? an overview, Exog Dermatol, 2004, 3(3), 154-160. 112 Weinkauf R, Habif S S and Bartolone J B, Cosmetic compositions containing hydroxy acids or retinoids as an anti-irritant/anti-sting agent, Eur Pat Appl, 1998, EP 858799 A2 19980819. 113 Weinkauf, R L, Habif S S and Bartolone J B, Trichodesma lanicum seed extract as an anti-irritant in compositions containing hydroxy acids or retinoids, US Pat, 1999, US 5855893 A 19990105. 114 Perianayagam J B, Sharma S K and Pillai K, Evaluation of antidiarrheal potential of Trichodesma indicum (L.) R. Br. root extract in rats, Methods Find Exp Clin Pharmacol, 2005, 27(8), 533-537. 115 Martínez-Pérez E F, Juárez Z N, Hernández L R and Bach H, Natural antispasmodics: Source, stereochemical configuration, and biological activity, Bio Med Res Int, 2018, 2018, 1-32. 116 Tanira M O M, Ali B H, Bashir A K, Wasfi I A and Chandranath I, Evaluation of the relaxant activity of some United Arab Emirates plants on intestinal smooth muscle, J Pharm Pharmacol, 1996, 48(5), 545-550. ABDELGAWAD et al.: AN OVERVIEW ON GENUS TRICHODESMA 117 Narendra K, Prasad M S, Joshi D S, Reddi K V, Swathi J, et al., Anti-diabetic activity of Trichodesma indicum (L) leaf extracts, J Biol Sci Opin, 2015, 3(6), 259-265. 118 Sayana S B, Khanwelkar C C, Nimmagadda V R, Dasi J M B, Chavan V R, et al., Evaluation of diuretic activity of alcoholic extract of roots of pharmacology section Cissampelos Pareira in albino rats, J Clin Diagn Res, 2014, 8(5), HC01-4. 347 119 Manani L M, Kakrani P and Saluja A K, Evaluation of diuretic activity of Trichodesma indicum (L.) R. Br. R. Br. in rats, Int J Pharm Bio Sci, 2014, 5(2), 129-133. 120 Lahon K and Das S, Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against paracetamol-induced liver damage in Albino rats, Pharmacogn Res, 2011, 3(1), 13-18. 121 Perianayagam J B, Sharma S K and Pillai K K, Evaluation of analgesic and antipyretic potential of Trichodesma indicum root extract in animal models, Int J Pharm Sci Lett, 2011, 1(1), 9-14.