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Phytochem Rev DOI 10.1007/s11101-017-9493-5 Trianthema portulacastrum L. (giant pigweed): phytochemistry and pharmacological properties Kumeshini Sukalingam . Kumar Ganesan . Baojun Xu Received: 18 November 2016 / Accepted: 3 February 2017 Ó Springer Science+Business Media Dordrecht 2017 Abstract Trianthema portulacastrum L. (Aizoaceae) commonly called as black pigweed or giant pigweed, which is a yearly herb, utilized as purgative, pain relieving, stomachic and provide as alternative heal for lung disease, cardiovascular disease, anemia and edema. In the Ayurvedic system of medicine, the plant is used in the treatment of inflammation in the peripheral organs, uteralgia and cough. Taking into account exploratory study, the present review aims to provide up-to date data about the routine uses, phytochemistry, and pharmacological actions of T. portulacastrum to explore their therapeutic value for future clinical settings. All data of T. portulacastrum were collected from library database and electronic search (ScienceDirect, Pubmed, and GoogleScholar). The different pharmacological information was gathered and orchestrated in a suitable spot on the paper. The genus Trianthema comprises of 64 species. Among them, the species of T. portulacastrum has been easily known for their customary uses. Phyto- Kumeshini Sukalingam and Kumar Ganesan they have contributed equally to the article as the first authors. K. Sukalingam  K. Ganesan  B. Xu (&) Food Science and Technology Program, Beijing Normal University–Hong Kong Baptist University United International College, 28, Jinfeng Road, Tangjiawan, Zhuhai 519085, Guangdong, China e-mail: baojunxu@uic.edu.hk chemical studies showed that T. portulacastrum included trianthamine, ecdysterone, flavonoid (5,2 dihydroxy-7methoxy-6,8 dimethyl flavone), leptorumol (5,7 dihydroxy-6,8 dimethyl chromone), and other intermediary bioactive compounds such as b-sitosterol, stigmasterol, and their b-glucopyranosides, bcyanin, 3,4-dimethoxy cinnamic acid, 5-hydroxy-2methoxy benzaldehyde, 3-acetyl aleuritolic acid, pmethoxy benzoic acid, and p-propoxy benzoic acid. The plant extracts showed significant antioxidant, antiinflammatory, hepatoprotective, antihyperglycemic, antimicrobial, and anticancer activities. The toxicity study conducted in animals and no noteworthy mortality found till 4 g/kg b.w. Taking into account on animal studies, T. portulacastrum have different bioactivities including antihyperglycemic, hepatoprotective, anticancer, antimicrobial and modulate different cellular signals related to control of oxidative stress and inflammation. The phytoconstituents of T. portulacastrum have a various potential to exact pharmacological benefits and possible chemotherapeutic mediator. Nevertheless, more support for such properties/dynamic constituents have been obtained from cellular and molecular studies, while clinical studies are as yet deficient. Since animal research do not constantly interpret to human conditions, additional clinical studies are also warranted to infer the full interpretation impact of T. portulacastrum for prevention of human diseases. Hence, future comprehensive clinical studies are required to warrant the therapeutic usefulness of the T. portulacastrum. 123 Phytochem Rev Graphical Abstract Keywords Trianthema portulacastrum  Phytochemistry  Pharmacology  Toxicity  Therapeutic uses Abbreviations T. portulacastrum NMR H2O2 DPPH ROS 123 Trianthema portulacastrum Nuclear magnetic resonance Hydrogen peroxide Diphenylpicrylhydrazyl Reactive oxygen species GSH GST SOD CAT GPx ALP DMBA NF-jB HDL WHO Glutathione Glutathione s-transferase Superoxide dismutase Catalase Gluathione peroxidase Alkaline phosphatase 7,12-Dimethylbenz[a]anthracene Nuclear factor High density lipoprotein World Health Organization Phytochem Rev Introduction Plants have been used as primary sources of medicine all over the world for more than 5000 years. It however, remains to lodge in an important position in traditional as well as modern systems of medicine. There are around 2000 flora species, which found to possess the medicinal properties in all these four indigenous systems of medicine, namely Siddha, Homeopathy, Ayurveda, and Unani. As shown by the report of the WHO, more than 80% of the world population depends on conventional systems of ethical dosage, generally plant based, to meet primary health care needs (Farnsworth et al. 1985; Bora et al. 2012). More than 7500 types of plants are judged to be utilized by different communities in veterinary and human health care. Approximately 1000 plants have been utilized in the Indian system of medicines. Efforts have been taken to evaluate the medicinal plants all through the nations, but a complete inventory is not available so far (Henry et al. 1987). These herbs are a noteworthy source of unknown dynamic substances with possible therapeutic effects. At present, thousands of plant metabolites are being effectively employed in the treatment of a diversity of diseases. The greater part of the supply of medication is found from wild plants. The therapeutic worth is dictated by the vicinity of phytochemical substances (secondary metabolites), which create a particular physiological potential of the human body. The medicinal plants are acquired from assorted sources, cultivated, wild state or of exotic origin. Their habit forma may be bushes, herbs, weeds or trees. The aim of this review is to give comprehensive information on the phytochemistry and pharmacological actions of T. portulacastrum to investigate their therapeutic value for potential clinical scenarios. Figure 1: a whole plant of T. portulacastrum L. Botanical description Trianthema portulacastrum L. is a flowering plant species in the ice plant family grown mostly in the wastelands, grows up to 30–60 cm long weed. It is yearly or fleeting indigenous weed of South Africa and commonly distributed in throughout Africa, Southeast Fig. 1 Whole plant of Trianthema portulacastrum L. and West Asia, India, Southern China, and tropical America. Nevertheless, the plant has no known centre of starting point. In India, Pakistan, Bangladesh and Sri Lanka, the weed is developed amid summer season along with the most important agricultural crops such as cotton, pulses, oilseeds, sugarcane, rice, maize, and wheat (Asghar et al. 2013) and causing a significant yield reduction in the crop production (Nayyar et al. 2001). T. portulacastrum is a prostrate, glabrous, succulent diffusely branched weed. Leaves are fleshy, scale like opposite, alternate, extipulate with membranous stipules. Flowers are regularly bisexual stamens vary from five to many and filaments are free or basically connate. Fruits are berry and loculicidal capsule. Taxonomy Regional name Kingdom: Plantae English-Horse Purslane Subkingdom: Tracheobionta Tamil-Sharunnai, Shavalai Super division: Spermatophyta Telugu: Galijeru Division: Magnoliophyta Kannada: Ambatimadu; Tella-galijeru Class: Magnoliopsida Hindi: Lalsabuni Subclass: Caryophyllidae Sanskrit: Punarnavi, Shvetapunarnava, Chiratika, Dhanapatra, Shvetamula, Upothaki Order: Caryophyllales Urdu: Narma 123 Phytochem Rev Taxonomy Regional name Traditional uses Family: Aizoaceae Pujabi: It sit Genus: Trianthema Marathi: Pundharighentuli Species: portulacastrum Arabic: Zaleya pentandra Trianthema portulacastrum has been practiced in the indigenous system of medicine for the obstruction of liver, asthma, amenorrhoea, dropsy, and beriberi (Chatterjee and Prakashi 1994). The infusion of the roots has cathartic and irritant properties and is employed as an abortifacient. But it indicates practically no activity on the confined uterus. The plant is acrid, hot, pain relieving, stomachic, and purgative, cures bronchitis, cardiovascular diseases, and various inflammations (Krithikar and Basu 1991). The leaves are diuretic and used in dropsy, edema, and ascities (Javed et al. 2000). A decoction of the plant is employed as a vermifuge and for the treatment of rheumatic arthritis. It is also an antidote to the alcoholic toxin. The plant is lithotropic for the kidney and bladder (Chopra et al. 1996). Indonesian: Subang-subang Thai: Phak bia hin Chinese: Shu mo shi ma chi xian Spanish: Verdolaga, Verdolaga blanca, Verdolaga de cochi, Verdolaga de hoja ancha Vietnamese: Sam bien, Co tam khoi, Rau sam gia The genus Trianthema comprises of 64 species. Among them, the species of T. portulacastrum has been easily known for their customary uses. The genus Trianthema and its species (IPNI 2017) 1. T. americana Gillies ex Arn. 20. T. galericulata Melville 2. T. anceps Thunb. 21. T. glandulosum Peter 3. T. argentina Hunz. & Cocucci 22. T. glaucifolium F. Muell. 42. T. pakistanense H. E. K. Hartmann & Liede 43. T. parvifolia E. Mey. 4. T. australe Melville 23. T. glinoides Pers. 44. T. patellitecta A. M. Prescott 5. T. camillei Cordem. 6. T. ceratosepala Volkens & Irmsch. 24. T. glossostigma F. Muell. 25. T. govindia Buch.-Ham. 45. T. pentandra L. 7. T. clavatum H. E. K. Hartmann & Liede 26. T. griseum O. Deg. & I. Deg. 47. T. polyandra Blume 27. T. hecatandra Wingf. & M. F. Newman 48. T. polysperma Hochst. ex Oliv. 9. T. corallicola H. E. K. Hartmann & Liede 28. T. hereroense Schinz 50. T. Procumbens Mill. 29. T. humifusum Thunb. 51. T. redimita Melville 10. T. corymbosum E. Mey. 30. T. humillimum F. Muell. 52. T. rhynchocalyptra F. Muell. 11. T. crystallinum (Forssk.) Vahl 31. T. hydaspicum Edgew. 53. T. rubens E. Mey. 12. T. cussackianum F. Muell. 13. T. cypseleoides (Fenzl) Benth. 32. T. kimberleyi Bittrich & Jenssen 54. T. salarium Bremek. 33. T. littorale Cordem. 55. T. salsoloides Fenzl ex Oliv 14. T. decandra L. 34. T. maidenii S. Moore 56. T. sanguinea Volkens & Irmsch. 15. T. diffusa Mill. 35. T. megaspermum A. M. Prescott 57. T. sedifolia Vis. 16. T. dinteri Engl. 17. T. dubium Spreng. ex Turcz. 36. T. monogyna L. 37. T. multiflorum Peter 58. T. sennii Chiov. 59. T. sheilae A. G. Mill. & J. A. Nyberg 18. T. flexuosum Schumach. & Thonn. 38. T. nigricans Peter 60. T. transvaalensis Schinz 19. T. fruticosum Vahl 39. T. nyasica Baker 61. T. triandra Wettst. 40. T. obcordata Wall. 62. T. triquetra Rottler & Willd. 41. T. oxycalyptra F. Muell. 63. T. turgidifolia F. Muell. 8. T. compactum C. T. White 46. T. pilosa F. Muell. 49. T. portulacastrum L. 64. T. ufoense H. E. K. Hartmann & Liede 123 Phytochem Rev The plant has impacted on blood pressure in the ileum of guinea pigs. An aqueous infusion of the whole plant was found to be a toxic for American cockroaches when infused into the circulatory system. The seeds were found harmful contaminants in food grains and other agricultural sources (The Wealth of India 1995). The nutritional study showed that the edible wild plant has excellent sources of fiber, proteins, thiamine, riboflavin, potassium, sodium, magnesium and iron (Khan et al. 2013). In light of exploratory assessment, the different concentrates of T. portulacastrum have been found to possess a various pharmacological activities such as analgesic (Shanmugan et al. 2007; Shivhare et al. 2012), antibacterial (Kavitha et al. 2014), antifungal (Nawaz et al. 2001), anticancer (Bhattacharya and Chatterjee 1999), anti-inflammatory (Vohora et al. 1983), antifertility (Pare et al. 2013), antioxidant (Kumar et al. 2005), antipyretic and hepatoprotective (Bishayee et al. 1996; Mandal et al. 1997a, b), nephroprotective (Karim et al. 2011), hypoglycaemic and hypolipidemic (Anreddy et al. 2010), diuretic (Asif et al. 2013), and mosquito larvicidal actions (Singh et al. 2011). Likewise, the study has affirmed that the T. portulacastrum has an antihepatotoxic effect based on the regulation of erythropoiesis and general unsusceptibility (Mandal et al. 1998), antioxidant enzymes (Mandal et al. 1997a, b), regulated hepatic oxidative DNA damage and chromosomal aberrations (Sarkar et al. 1999). The ethanolic extract of T. portulacastrum leaves has a potential of hepatoprotective against hepatic damage caused by paracetamol and thioacetamide (Kumar et al. 2004), rifampicin (Mehta et al. 2003), aflatoxin B1 (Banu et al. 2009a, 2009b) and high fat diet (Sunder et al. 2010a, b, c) in animal models. Phytochemistry The methanolic extract of T. portulacastrum leaves contains carbohydrates, protein, volatile oils, glycosides, saponins, flavonoids, alkaloids (Verma 2011). Trianthamine and punarnavine have been reported from this plant extracts (Wealth of India 1976). It also contains ecdysterone, which is potential chemosterilant (Banerji et al. 1971; Tripathi 2004) and moulting hormone activity, gives a full pupation response for larvae of house fly (Kumar et al. 2004). T. portulacastrum contains mostly vitamins (B3 and C), carotenes (0.23%) and various concentrations of minerals [calcium (0.3%), phosphorus (0.13%), magnesium (0.2%), iron (50 ppm), copper (8 ppm), zinc (30.0 ppm), manganese (50 ppm) and crude protein (1.5%)] (Bharathidhasan et al. 2007; Khare 2006). Fresh plant leaves contains branched chain hydrocarbon, which has been isolated and characterized from the surface wax through gas liquid chromatography (Singh et al. 1982). The lipid fractions and fatty acid composition of seed oil of T. portulacastrum (Ashraf and Riaz 1996) has listed in the Table 1. Total phenolic compounds were isolated at various concentrations in root (6–10%), shoot (5–7%), and leaf (5–9%) portions of crude hydrolysates of T. portulacastrum (Yaqoob et al. 2014). Kokpol et al. (1997) isolated flavonoid (5,2 dihydroxy-7methoxy6,8 dimethyl flavone), leptorumol (5,7 dihydroxy-6,8 dimethyl chromone), and other active compounds such as b-sitosterol, stigmasterol and their b-glucopyranosides, 3,4-dimethoxy cinnamic acid, b-cyanin, 3-acetyl aleuritolic acid, 5-hydroxy-2-methoxy benzaldehyde, p-propoxy benzoic acid, and p-methoxy benzoic acid. Al Sherif and Gharieb (2011) isolated quercetin and other numerous benzoic and cinnamic acid derivatives, such as p-hydroxy benzoic acid, protocatechuic acid, vanillic acid, ferulic acid, caffeic acid, 3,4-dimethoxy cinnamic acid, o-coumaric acid and pyrogallol. Beta cyanin, the predominant widespread red coloured flavonoid occur in several plant species, has also been accounted in T. portulacastrum (Sunder et al. 2009). Nawaz et al. (2001) isolated four terpenoids from the chloroform extract of T. portulacastrum, which employs as antifungal agents. Based on twoTable 1 The lipid fractions and fatty acid composition of seed oil of T. portulacastrum L. Lipids Composition Percentage Total lipids Neutral lipids 95.2 Polar lipids Neutral lipids 4.8 Sterol esters 4.0 Triglycerides 84.5 Free fatty acids 1.8 Diglycerides 2.5 Monoglycerides 1.6 Hydrocarbons 0.3 123 Phytochem Rev dimensional NMR techniques, the plant has found an antifungal substance, namely trinthenol (15-hydroxymethyl-2, 6, 10, 18, 22, 26, 30-heptamethyl-14methylene-17-hentriacontene), benzaldehyde, benzoic acid derivatives, and pentacyclic terpenoids. Trianthenol comprises 40-carbonated compounds with 8 isoprene units and a trans-double bond, which is accountable for its E-configuration. In addition, bcarotene has also been identified from the organic solvents (Khare 2007). The chemical structure of typical phytochemical constituents present in T. portulacastrum was listed in the Table 2. Pharmacological uses Trianthema portulacastrum has various phytochemical compositions, which recuperate or control many metabolic diseases like diabetes, jaundice, inflammation, nephrological disorders, asthma, anemia, Table 2 Major phytochemical constituents isolated from T. portulacastrum L. Beta-ecdysterone Leptorumol 3-Acetyl aleuritolic acid Beta sitosterol Stigmasterol p-Methoxy benzoic acid 5-Hydroxy-2-methoxy benzaldehyde 3,4-Dimethoxy cinnamic acid p-Propoxy benzoic acid 7-Hydroxy-3-methylflavone Pyridine-3-carboxyli c acid Ascorbic acid 123 Phytochem Rev ascities, and malignancy. T. portulacastrum has potential pharmacological properties as complementary medicine and utilized in various formulations implied for antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, hypoglycaemic, anticancer, and antimicrobial agents. The detailed information about dose range, type of extract used, route of administration, the model used, positive and negative controls, study duration and other pharmacological results have made based on the experimental research study in vivo and in vitro according to the appropriate title. Antioxidant potential Oxidative stress plays a crucial part in the pathogenesis of numerous degenerative diseases like diabetes, atherosclerosis, osteoporosis, rheumatoid arthritis, Parkinsonism, Huntington, Alzheimer, muscular dystrophy and cancer (Kaneto et al. 2010; Moura et al. 2010; Patten et al. 2010; Queen and Tollefsbol 2010). T. portulacastrum possessed antioxidant activity by reducing lipid peroxidation and promoting the scavenging of hydrogen peroxide (H2O2) and diphenyl picrylhydrazyl (DPPH) free radicals (Badmanaban et al. 2010; Sunder et al. 2010b). In vivo experimental animal models and in vitro studies provided that T. portulacastrum exerts potent antioxidant activities, as summarized in Table 3. Lipid peroxidation is one of the essential indications of oxidative damage initiated by reactive oxygen species (ROS) and it has been connected with altered membrane structure and inactivation of catalysts. It is setting forth to drag of a hydrogen atom from polyunsaturated fatty acids in the plasma membrane (Shen et al. 1994). The expansion of lipid peroxides might come from a spontaneous generation of free radicals and which was overcome by the administration of ethanolic extract of T. portulacastrum (Kumar et al. 2005). GSH and GST are non-enzymatic antioxidants involved in the enzymatic detoxification of ROS. The amalgamation of intracellular GSH and GST activities were upgraded by ethanolic extract of T. portulacastrum leaves and silymarin that have the key role in mitigating toxicant incited oxidative stress and succeeding liver damage (Kumar et al. 2005). Note worthy antioxidant enzymes such as SOD, CAT, and GPx appears the first line of defense against ROS and a drop-off in their activities was observed with toxicanttreated animals (Banu et al. 2009a). Ethanolic extract of T. portulacastrum leaves promotes the GSH levels, resulting in the increase in SOD activity, thereby preventing the deleterious effect of super oxide radicals. Thus T. portulacastrum directly influences the activities of SOD and CAT. Trianthema portulacastrum was found to decrease the generation of ROS in the liver and kidney by restoring endogenous antioxidant enzyme activities (Banu et al. 2009b; Karim et al. 2011). These findings indicated that the T. portulacastrum has potent antioxidant activity, suggesting that it can be applied as a complementary medicine to anticipate oxidative damage actuated various degenerative and metabolic diseases. Hepatoprotective potential Administration of ethanolic extracts of T. portulacastrum in a dose-dependent manner created a decrease in the activity of hepatic marker enzymes in serum, which may be on the issue of stabilizing the cell membrane and restore of hepatic tissue damage caused by toxicants like aflatoxin, paracetamol, thioacetamide (Kumar et al. 2004). Alkaline phosphatase (ALP) is a hepatic enzyme typically discharged through bile. In liver injury due to hepatotoxin, discharge of bile diminished by the liver, which is reflected in their increased levels in serum (Kim et al. 2006; Kumar et al. 2006) and this enzyme level was nullified by the administration of T. portulacastrum in rats (Kumar et al. 2004). Hyperbilirubinaemia is a sensitive test for liver function and severity of necrosis, which improves the binding, conjugation and discharge of liver cell that is relative to the rate of erythrocyte degeneration (Singh et al. 1998; Meshkibaf et al. 2006). Exhaustion of high bilirubin level accompanying with a low level of ALP in the serum treated with T. portulacastrum recommended the possibility of phytotherapeutic constituents of the plant extracts being able to stabilize biliary dysfunction of rat liver. The hepatoprotective activity of T. portulacastrum against heptotoxin may be because of the vicinity of the dynamic metabolite in T. portulacastrum which in turn diminished drug metabolizing enzymes through binding with RNA 123 Phytochem Rev Table 3 Summary of in vivo and in vitro studies of antioxidant potentials of T. portulacastrum L. Model TP extract Dose/ route/duration Negative control Investigation Results References – Methanolic extract leaf, root, and shoot 1, 10, 100, 1000, 2000, and 5000 (lg/ml) – (1) DPPH antiradical capacity TP as potential source of valuable antioxidants Yaqoob et al. (2014) Wistar albino rats Ethanolic extract of leaves 100, 200 mg/ kg b.w/p.o; 2 weeks Paracetamol (3 g/kg bw) and thioacetamide (150 mg/ kg bw) (1) TP increased liver glutathione, liver Na–KATPase (2) TP increased blood GSH, SOD, CAT, GSH-Px, GST, GSH-R TP exerted hepatoprotective and antioxidant potential Kumar et al. (2005) – Aqueous and ethanolic extract of leaves 10 ll – (1) DPPH antiradical capacity TP as potential source of valuable antioxidants Rattanata et al. (2014) Male wistar albino rats Ethanolic extract 200 and 400 mg/kg b.wt Ethylene glycol 0.75% and ammonium chloride 1% (1) TP significantly restored urinary (urinary volume, calcium, oxalate, phosphate, magnesium, and phosphate) and serum (calcium, creatinine, uric acid, BUN) and antioxidants parameters (SOD, CAT, MDA) TP as potential source of valuable antioxidants Lakshmi et al. (2014) – Methanolic extract of leaves 10 ll – (1) DPPH radical scavenging assay TP as potential source of valuable antioxidants Badmanaban et al. (2010), Sunder et al. (2010b) (2) Ferric reducing antioxidant power (3) inhibit linoleic acid peroxidation (2) Ferric reducing power (2) Hydrogen Peroxide Scavenging assay (3) Nitric Oxide scavenging assay Wistar albino rats Methanolic extract of leaves 100, 200 mg/ kg b.w/p.o; 2 weeks High fat diet (1) TP increased the liver catalase, superoxide dismutase, glutathione (2) TP decreased lipid peroxide (malondialdehyde) levels TP as potential source of valuable antioxidants and antihyperlipidemic Sunder et al. (2010a) – Methanolic extract of leaves 10–50 ll – (1) DPPH radical scavenging assay TP has as potential of antioxidants Guha et al. (2011) (2) ABTS radical scavenging activity (3) Ferric reducing antioxidant property (4) DNA damage inhibition efficiency polymerases and thereby cessation of protein and nucleic acid synthesis (Bowman and Rand 1982). In vivo, experimental animal models provided that T. portulacastrum exerts potential hepatoprotective activities, as summarized in Table 4. 123 Anti-inflammatory potential The extract also successfully suppressed the inflammation delivered by mediators namely histamine, serotonin, and prostaglandins. T. portulacastrum Phytochem Rev Table 4 Summary of in vivo studies of hepatoprotective potentials of T. portulacastrum L. Model TP extract Dose/ route/duration Negative control Investigation Results References Wistar albino rats Methanolic extract 100, 200 mg/ kg b.w/p.o; 2 weeks 4% Cholesterol, 1% cholic acid and 0.5% thiouracil (CCT) (1) TP reduced serum LDH, AST, ALT, ALP, Bil and creatinine TP exerted antihepatotoxic potential and reduce glomerulosclerosis Sunder et al. (2010c) Wistar albino rats Ethanolic extract of leaves 100, 200 mg/ kg b.w/p.o; 2 weeks Aflatoxin B1 (1 mg/kg bw, p.o) (1) TP reduced serum LDH,ALP, AST, ALT, lipid peroxide levels TP exerted antihepatotoxic potential and reduced Aflatoxin B1-induced hepatotoxicity Banu et al. (2009a) TP exerted antihepatotoxic potential and reduced Aflatoxin B1-induced hepatotoxicity Banu et al. (2009b) (2) TP increased SOD, CAT, GSH-Px, GSH-R, G6PD, GST (3) TP enhanced the level of GSH, vitamin C, vitamin E (1) TP decreased SGOT, SGPT, ALP and Bil Wistar albino rats Ethanolic extract of leaves 100, 200 mg/ kg b.w/p.o; 2 weeks Aflatoxin B1 (1 mg/kg bw, p.o) Wistar albino rats Ethanolic extract of leaves 100, 200 mg/ kg b.w/p.o; 3 weeks Paracetamol (3 g/kg bw) and thioacetamide (150 mg/kg bw) (1) TP decreased SGOT, SGPT, ALP and Bil TP exerted hepatoprotective and reduced paracetamol and thioacetamide intoxication Kumar et al. (2004) Wistar albino rats Alcoholic extract of aerial parts 100 mg/kg b.w/p.o; 2 weeks Paracetamol (3 g/kg bw) and rifampicin (1 g/kg bw) (1) TP decreased SGOT, SGPT, ALP and Bil TP exerted hepatoprotective and reduced paracetamol and rifampicin intoxication Mehta et al. (2003) Wistar albino rats Ethanolic extract of leaves 100, 200 mg/ kg b.w/p.o; 2 weeks Paracetamol (3 g/kg bw) and thioacetamide (150 mg/kg bw) (1) TP increased of liver GSH, liver Na–KATPase TP exerted hepatoprotective and reduced paracetamol and thioacetamide intoxication Kumar et al. (2005) Carbon tetrachloride (1) TP decreased SGOT, SGPT, ALP, glutamate dehydrogenase, sorbitol dehydrogenase, Bil and urea. (2) TP decreased in the activities of plasma membrane enzymes cglutamyl transpeptidase and 50 -nucleotidase and lysosomal enzymes acid phosphatase and acid ribonuclease in hepatic tissue TP exerted antihepatotoxic and cytoprotection on carbon tetrachloride intoxication Mandal et al. (1997a, b) Swiss albino mice Ethanolic extract of leaves 100, 150 mg/ kg b.w/p.o; 2 weeks (2) TP enhanced blood GSH, SOD, GSH-Px, GST, GSH-R 123 Phytochem Rev Table 4 continued Model TP extract Dose/ route/duration Negative control Investigation Results References Swiss albino mice Ethanolic extract of leaves 100, 150 mg/ kg b.w/p.o; 2 weeks Carbon tetrachloride (1) TP decreased hepatocellular necrosis, severe anaemia, leucopaenia, lymphocytopaenia, neutrophilia, eosinophilia and haemoglobinaemia TP exerted hepatoprotective and involved in modulating several erythropoiesis factors and boosting host immunity Mandal et al. (1998) (2) TP enhanced plasma albumin and globulin Swiss albino mice Ethanolic extract of leaves 150 mg/kg b.w/p.o; 13 weeks Carbon tetrachloride (1) TP protects liverspecific structural-type chromosomal anomalies TP has the potential of hepatoprotective and able to counteract oxidative injury to DNA in the liver Sarkar et al. (1999) Swiss albino mice Ethanolic extract of leaves 50, 100, 150 mg/kg b.w/p.o; 2 weeks Alcohol-carbon tetrachloride (1) TP elevated serum enzymatic activities of GOT, GPT, LDH, ALP, sorbitol and glutamate dehydrogenase TP has the potential of hepatoprotective against hepatocellular injury Bishayee et al. (1996) TP exerted hepatoprotective activity mediated through a marked inhibition of CCl4 induced hepatic lipid peroxidation with a concurrent modulation of GSH status and the activities of antioxidant defense enzymes in mouse liver Mandal et al. (1997a, b) (2) TP decreased of hepatic malondialdehyde formation and increased GSH Swiss albino mice Ethanolic extract of leaves 100, 150 mg/ kg b.w/p.o; 5 weeks Carbon tetrachloride (1) TP decreased lipid peroxidation, increase hepatic-reduced glutathione (GSH) level and decrease in their oxidized glutathione (GSSG) level; increase in the activity of GSH-R, CAT, GSH-Px, GST in liver exhibited a significant inhibition against histamine and 5-hydroxy histamine affected hind paw oedema, which demonstrates that the extracts restrains its anti-inflammatory action by methods of either inhibiting the synthesis, release or activity of inflammatory mediators might be involved in inflammation and it can be proposed that the inflammatory activity is potentially backed by its anti-histaminic activity (Saravanan et al. 2004). Chronic inflammation is a response arising when the intense reaction is inadequate to eliminate proinflammatory agents. Carrageenan affects protein rich exudation containing a huge number of neutrophils. The T. portulacastrum extract adequately stifled the inflammation produced by carrageenan-induced edema. 123 The dynamic constituents of T. portulacastrum possess anti-inflammatory potential (Shivhare et al. 2012). Based on the experimental information, T. portulacastrum exerts inhibition of 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary tumorigenesis at least, to some degree, by suppression of inflammatory stress response. T. portulacastrum averts DMBA induced breast neoplasia by antiinflammatory mechanisms intervened through concurrent and differential modulation of two interconnected molecular circuits, to be specific NF-jB and Nrf2 signaling pathways (Mandal and Bishayee 2015). In vivo, experimental animal models provided that T. portulacastrum exerts potential antiinflammatory activities, as summarized in Table 5. Phytochem Rev Antihyperglycemic potential The experimental study recommended that the methanolic extract of T. portulacastrum had significant hypoglycemic, antihyperglycemic, hypolipidaemic activities in normal, alloxan and streptozotocin-induced diabetic rats (Sunder et al. 2009; Anreddy et al. 2010). Fasting blood glucose level in diabetic rats is a noteworthy parameter for observing diabetes and the outcomes demonstrated that T. portulacastrum brought about hypoglycemia and antihyperglycemic impact by diminishing the fasting blood glucose level. The noteworthy reduction of fasting blood glucose in T. portulacastrum administered diabetic rats may be due to the enhanced secretion of insulin from b-cells of the pancreas or incitement of the residual pancreatic mechanism, presumably by increasing peripheral usage of glucose (Sunder et al. 2009). Besides, the supplementation of T. portulacastrum produced a significant, valuable impact on the lipid profile in normal and diabetic rats by reducing triglycerides, total cholesterol and increasing HDL levels significantly. This impact may be because of low activity of cholesterol biosynthesis enzymes and or low level of lipolysis, which are under the control of insulin (Sharma et al. 2003; 2009). The administration of T. portulacastrum may cause the recovery of the b-cells of the pancreas and potentiating of insulin secretion from surviving bcells or incitement of more insulin secretion and consequently diminishes the blood glucose level may prevent lipid peroxidation and control of lipolytic hormones in STZ induced diabetic rats (Anreddy et al. 2010). In vivo, experimental animal studies provided that T. portulacastrum exerts potential antihyperglycemic activities, as summarized in Table 6. Antimicrobial potential In vitro investigations of T. portulacastrum has an antimicrobial impact against gram positive and gram negative bacteria and various fungi (Kavitha et al. 2014; Mohammed et al. 2012). T. portulacastrum Table 5 Summary of in vivo studies of anti-inflammatory potentials of T. portulacastrum L. Model TP extract Dose/ route/duration Negative control Investigation Results References Wistar albino rats Ethanolic extract 50, 100 and 200 mg/kg b.w 7,12Dimethylbenz(a) anthracene (DMBA) (1) TP down regulated the expression of inflammatory enzymes such as cyclooxygenase-2 and heat shock protein 90, blocked the degradation of inhibitory kappa B-alpha, hampered the translocation of nuclear factorkappa B from cytosol to nucleus and up regulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis TP prevents DMBAinduced breast neoplasia by antiinflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NF-jB and Nrf2 signaling pathways Mandal and Bishayee (2015) Swiss albino mice and Swiss Wistar albino rats Chloroform extract 50, 100, 200 mg/kg b.w/p.o; 8 h Carrageenan (30 mg/kg b.w) (1) TP exhibited significant inhibition on the hind paw oedema TP exerted antiinflammatory potential Sunder et al. (2009) 123 Phytochem Rev exerted its antibacterial effects due to its ability to limit bacterial development by its phytochemicals and enhance the synergistic impacts of antibiotics and thereby decreasing the probability of resistance to drugs (Kavitha et al. 2014). These antimicrobial activities of T. portulacastrum have been proposed as promising applications in wellbeing protection in order to avoid communicable diseases (Nawaz et al. 2001; Rattanata et al. 2014). T. portulacastrum exhibited dose and time dependent anthelmintic effects on live worms as well as egg hatching (Hussain et al. 2011). Summary of in vitro studies of antimicrobial potentials of T. portulacastrum demonstrated in the Table 7. T. portulacastrum showed more effective mosquito larvicidal action in acetone extract compared to aqueous extract. T. portulacastrum extracts have phytochemicals which are to be used for the progress of larvicide against disease vectors (Singh et al. 2011). Anticancer potential Three extracts (viz., aqueous, ethanolic and chloroform) of T. portulacastrum found to decrease the incidence, multiplicity, and visible size neoplastic nodules in the liver and altered microscopic hepatic cell foci stimulated by potent hepatocarcinogen (diethylnitrosamine) in rats. These three extracts tweaked phase I and II drug metabolism in hepatic enzymes and antioxidant protection in diethylnitrosamine induced animals (Bhattacharya and Chatterjee 1998a, b). The chloroform extract of T. portulacastrum exhibited an inhibitory effect against rat hepatocellular carcinogenesis induced by phenobarbital (Bhattacharya and Chatterjee 1999). Ethanolic extract of T. portulacastrum exhibited a prominent suppression of DMBA initiated breast tumor incidence, entire tumor burden, and normal tumor weight with no lethal sign in rats (Bishayee and Mandal 2014). Further study has developed that T. portulacastrum in a dose-dependent manner induced apoptosis and forestalled irregular cell proliferation, proapoptotic protein Bax, antiapoptotic protein Bcl-2 and decreased enacted Wnt/b-catenin signaling in breast tumors (Bishayee and Mandal 2014). In light of empowering results, the mammary tumour-inhibitory effect of T. portulacastrum has also performed (Bishayee and Mandal 2014). Anti-inflammatory mechanisms of T. portulacastrum executed by observing proinflammatory and stress markers, namely cyclooxygenase-2, heat shock protein 90, and inflammation-regulatory signaling pathways, namely nuclear factor-jB and nuclear factor erythroid 2-related factor 2 in DMBA-induced mammary gland neoplasia in rats (Mandal and Bishayee 2015). Summary of in vivo and in vitro studies of anticancer potentials of T. portulacastrum demonstrated in the Table 8. Toxicity assessment Oral acute toxicity study has been conducted in either sex of rats and mice using different dosages of methanolic and ethanolic extracts of T. portulacastrum. There was no noteworthy mortality originated till 4 g/kg b.w., therefore, both extracts were found to Table 6 Summary of in vivo studies of antihyperglycemic potentials of T. portulacastrum L. Model TP extract Dose/ route/duration Negative control Investigation Results References Wistar albino male rats Methanolic extract 100, 200 mg/ kg b.w/p.o; 8h Streptozotocin (30 mg/kg b.w) (1) TP reduced blood sugar TP exerted antihyperglycemic potential and reduce blood glucose within 2 h Sunder et al. (2009) Wistar albino male rats Methanolic extract 100, 200, 300 mg/kg b.w/p.o; 7 days Alloxan (120 mg/kg b.w) (1) TP reduced blood sugar TP exerted antihyperglycemic and hyperlipidemic potential and reduce blood glucose and lipid profile within 7 days Anreddy et al. (2010) 123 (2) TP decreased total cholesterol, triglycerides and HDL Phytochem Rev Table 7 Summary of in vitro studies of antimicrobial potentials of T. portulacastrum L. Microbial Strains Methods Dose/extract Investigation Results References Bacterial—E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus vulgaris, Klebsiella pneumonia Bacterial assay 20 ll/ aqueous, methanol and chloroform extracts Antibacterial activity by agar well and disc diffusion methods revealed that the zone of inhibition was found to be maximum in the methanolic extract followed by the chloroform extract. Aqueous extract showed the least antibacterial activity. The methanol and chloroform extracts showed less than 100% inhibition against A. niger, A.fumigatus, Rhizopus and Candida albicans (1) Methanolic extract has a variety of phytochemical compounds Kavitha et al. (2014) 20 ll/ aqueous, and ethanol extracts Ethanolic extracts had 20.10% inhibition against Shigella spp (1) The extract have phenolic and flavonoids Rattanata et al. (2014) 20 ll/hhexane, n-butanol, chloroform and ethyl acetate fractions Antibacterial activity by agar well diffusion method revealed that the zone of inhibition was found to be maximum in n-hexane fractions against Staph. aureus, B. Subtilis. Antifungal activity was found in n-hexane fractions against Candida Albicans, (2) TP has a excellent antibacterial and activities (1) TP has a excellent antibacterial and antifungal activities Mohammed et al. (2012) Fungal—Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Mucor and Rhizopus (1) Disc diffusion method (2) Agar well diffusion method (3) Determination of minimum inhibitory concentration (4) Determination of minimal bactericidal concentration (2) TP has a excellent antibacterial and antifungal properties Fungal assay (1) Agar plug method (2) Spore germination inhibition assay (3) Determination of minimum fungicidal concentration Shigella flexneri Bacterial Staph. aureus, B. subtilis Pseudomonas aeruginosa, Salmonella typhimurium, E.coli Fungal Candida albicans, A. fumigatus Penicillium italicum Fusarium, Fusarium s. Cucurbitae, Fusarium niveum, Botrytis cinerrea (1) Paper disc diffusion method Bacterial Agar well diffusion method Fungal Agar well diffusion method 123 Phytochem Rev Table 7 continued Microbial Strains Methods Dose/extract Investigation Results References Candida Albicans, A. fumigatus Agar well diffusion method 20 ll/ chloroform extract (1) An antifungal tetraterpenoid named trianthenol 1 has been isolated. Its structure was established as 15-hydroxymethyl2,6,10,18,22,26,30heptamethyl-14methylene-17hentriacontene on the basis of spectroscopy and mass and twodimensional NMR techniques (1) A benzaldehyde derivative 2, a pentacyclic triterpenoid 3 and benzoic acid derivatives 4–5 are also reported Nawaz et al. (2001) (1) TP has a excellent antifungal activities Sheep gastrointestinal nematodes (Haemonchus contortus, Trichostronglyus spp., Oesophagostomum columbianum and Trichuris ovis) Adult motility assay (AMA) and egg hatch test 1–8 g/kg Aqueous and methanolic extracts TP exhibited dose and time dependent anthelmintic effects on live worms as well as egg hatching TP possess strong anthelmintic activity in vitro and in vivo Hussain et al. (2011) Mosquito larvicidal properties against four vector species (Anopheles culicifacies, Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti) Larval bioassay test 1.0, 0.75, 0.75 and 1.0% respectively/ aqueous and acetone extracts TP exhibited more effective mosquito larvicidal action in acetone extract compared to aqueous extract TP possess strong mosquito larvicidal properties Singh et al. (2011) be harmless up to the dose level of 4 g/kg b.w. (Tripathi 2004; Anreddy et al. 2010). There is no known unusual behavior found in either sex of albino mice while intraperitoneal administration of ethanolic extracts of T. portulacastrum leaves (Kumar et al. 2004; Shanmugan et al. 2007). Conclusion Based on the animal model investigation, T. portulacastrum has been found to regulate cell signals involved in the control of oxidative stress and inflammation. Furthermore, its activity on the liver as well as kidney and significantly diminished hepatocellular necrosis, restored urinary constituents, increased albumin, globulin values, and improved serum antioxidant parameters. T. portulacastrum has anticancerous impacts in normal cells and proapoptotic effects in malignancy tumors recommend 123 (1) TP extracts have phytochemicals which is to be used for the development of larvicide against disease vectors positive pharmacological advantages as a possible chemotherapeutic mediator (Yamaki et al. 2016). In any case, more support for such properties/dynamic constituents has been acquired from cellular and molecular studies, while clinical studies are as yet inadequate. Since animal research doesn’t generally interpret to human circumstances, additional clinical studies are likewise to justify comprehending the full interpretation effect of T. portulacastrum for human disease prevention. Subsequently, futures far-reaching clinical studies are required to warrant the therapeutic convenience of the T. portulacastrum. Acknowledgements Funding was provided by Beijing Normal Unveristy-Hong Kong Baptist University United International College (Grant No. R201624). Compliance with ethical standards Conflict of interest interest. Authors declared that no conflicts of Model TP extract Dose/ route/duration Negative control Investigation Results References Male Sprague— Dawley rats Choloroform extract 100 mg/kg b.w/p.o; 22 weeks diethylnitrosoamine (DENA) (1) Morphometric evaluation-TP reduced fraction of the incidence, numerical preponderance, and multiplicity and size distribution of visible pre-neoplastic nodules TP has a potential of anticarcinogenic Bhattacharya and Chatterjee (1998a, b, 1999) (2) TP reduced liver cell foci/cm2 and focal area (3) TP decreased the percentage of liver parenchyma occupied by foci 123 Male Sprague— Dawley rats Aqueous ethanol and Choloroform extract 100 mg/kg b.w/p.o; 22 weeks diethylnitrosoamine (DENA) (1) TP increased glutathione levels and the levels of Phase I (cytochrome P-450 monooxygenase) and Phase II (UDPGT) enzymes TP exerted as strong anticarcinogenic compounds Bhattacharya and Chatterjee (1998a, b) Wistar albino rats Ethanolic extract 50, 100 and 200 mg/kg b.w 7,12Dimethylbenz(a)anthracene (DMBA) (1) TP suppressed proliferating cell nuclear antigen and cyclin D1 expression, induced apoptosis, upregulated proapoptotic protein Bax, downregulated antiapoptotic protein Bcl-2 and diminished the expression of nuclear and cytosolic b-catenin in mammary tumors. TP exerted chemopreventive effect in the classical DMBA model of breast cancer by suppressing abnormal cell proliferation and inducing apoptosis mediated through alteration of Bax/Bcl-2 ratio Bishayee and Mandal (2014) Wistar albino rats Ethanolic extract 50, 100 and 200 mg/kg b.w 7,12Dimethylbenz(a)anthracene (DMBA) (1) TP down regulated the expression of cyclooxygenase-2 and heat shock protein 90, blocked the degradation of inhibitory kappa B-alpha, hampered the translocation of nuclear factor-kappa B from cytosol to nucleus and up regulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis TP prevents DMBA-induced breast neoplasia by anti-inflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NFjB and Nrf2 signaling pathways Mandal and Bishayee and (2015) Phytochem Rev Table 8 Summary of in vitro studies of anticancer potentials of T. portulacastrum L. 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