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Received : 26-11-2020

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Get Permission Santhosha DU, Manasa R, Vishwanath S, Naik R, and Mahesh MS: Hepatoprotective activity of Boerhaavia diffusa L


Introduction

Boerhaavia diffusa L. known as Punarnava in Ayurveda and ‘Hog weed’ in English, belonging to the family of Nyctaginaceae. In Ayurveda means one which renews our body and helps to regain the youthness. The genus Boerhavia diffusa (often spelled as Boerhaavia) was named in honour of Hermann Boerhaave (1668–1738), an Eighteenth century Dutch botanist, humanist and physician at the University of Leiden, while the species got the name from typical diffuse branching. The botanical name of the plant is often written in the literature as Boerhaavia diffusa,1 but Linnaeus Latinized Boerhaave's name to Boerhavius and adopted the spelling Boerhavia diffusa, which is the correct spelling to be used.2 Boerhavia is distributed in the temperate, tropical and sub-tropical regions like Asia, U.S.A., and Africa. In India it is found throughout the warmer parts of the country and grows up to 2000 m in the Himalayas.3 Mainly six species are found in India out of 40 i.e., B. diffusa, B. chinensis, B. erecta, B. repens, B. rependa, and B. rubicunda.

The herbal medicine has evolved and changed through the years. Similarly, it has been used in raw form as well as extract form in various disorders.4 In Ayurveda, this drug is known to be used as Mootrala (diuretic), Sothaghna (Anti-inflammatory), Kasahara (Antitussive), jwarahara (antipyretic), Rasayana (rejuvenator). The roots have clinical, pharmacological and antimicrobial properties which helps to cure many diseases like diabetes, liver diseases and kidney problems. The antiaging attributes also incorporates being Adaptogenic, Antioxidant and as Immunomodulator. It also has ethno botanical uses as leaves are used as vegetable and juice is made from the roots which cures asthma, urinary disorders, rheumantism etc.,

A number of phytochemicals e.g. flavonoids: (C-methylflavone, 5,7-dihydroxy-3’,4’-dimethoxy- 6,8- dimethylflavone, 3,5,4′- dihydroxy-6,7-dimethoxyflavone, 6’, 5’-dimethoxy-5,7, 3-trihydroxyflavone, borhavone, 3,3’,5-trihydroxy-7-methoxyflavone, 4,7-dihydroxy-3’-methylflavone), alkaloids: punarnavine, glycosides: (punarnavoside, eupalitin 3-O-β-D-galactopyranosyl-(1’2’)-O-β-D-galactopyranoside, 3,4- dimethoxyphenyl-1-O-β-D apiofuranosyl-(1’3’)-O-β-D-glucopyranoside), rotenoids:(boeravinone A-H), steroids, triterpenoids, lipids, lignans, carbohydrates, proteins, and glycoproteins etc., have been reported from the herb. Several researchers have confirmed biological, pharmacological and clinical activities of the plant and its phyto-constituents.5, 6, 7, 8

Pharmacognosy

Scientific Name: Boerhaavia diffusa Linn.    

Kingdom: Plantae

Phylum: Angiosperms

Division: Magnoliophyta

Class: Magnoliopsida

Order: Caryophyllales

Family: Nyctaginace (four o’clock)

Group: Dicotyledons

Vernacular names

It is called by several different names owing to its wide distribution throughout the world that is, Alena (Hawaii); Ervatostao, Agarra- pinto and Amarra-pinto (Brazil); Hogweed (Barbados); Red spiderling, Spreading hogweed (English); Huang Xi Xin (Chinese); Ipecacuanha de Cayenne (French Guiana); and Hierba de cabra (Spanish).

In Indian languages

Sanskrit: Punarnava, Raktakanda, Shothaghni, Varshabhu

Kannada: Kommegida, Sanadika, Kommeberu and Komma

Telugu: ErraGaligeru, Atikamamidi, Punarnava,

English: Spreading Hog weed (Red), horse purslane (White)

Oriya: Lalapuiruni, Nalipuruni;

Assamese: Ranga Punarnabha

Kashmiri: VanjulaPunarnava;

Hindi: Snathikari, Gadapurna, Lalpunarnava

Gujarati: Dholiasaturdo, Motosatoda, Dholisaturdi,

Tamil: Mukaratee-Kirei, Mukurattai (Shihappu)

Malayalam: ChuvannaTazhutawa

Marathi: Tambadivasu, Ghetuli, Vasuchimuli, Satodimula, and Khaparkhuti;

Bengali: Punurnava, RaktaPunarnava

Punjabi: ltcit (Ial), Khattan;

Hepatoprotective Activity

Liver is an important vital organ of the body and protects the body against xenobiotics and it is highly targeted by many toxic and harmful chemicals. Many studies have shown the hepatoprotective activity of BD.9 Researchers studied that protection against paracetamol induced hepatotoxicity for BD extracts. Jaundice is a disease for which BD has been constantly used either in traditional system of medicine or in ethnopharmacological reports. Also studied against liquor toxicity of liver. Some of the phytoconstituents present in the plant are also responsible for the protection of liver from the foreign bodies/ substances

Invitro studies

The hydro alcoholic extract of roots of Boerhavia diffusa (HEBD) exhibited a significant protective action on liver. 1% HEBD is mixed with 0.5% of 1.0 M magnesium acetate to prepare equal amount of supernatant solution and poured into the gels set in the test tubes in aseptic medium. The growth of crystals without and with herbal extracts was monitored at regular time intervals. The inhibition of crystals increased as the concentration of BD increases in the gel media as well as the dissolution of crystals at the gel-liquid interface increases. The de-fragmentation of some grown crystals was also noticed.

Animal studies

Olaleye and co-workers evaluated the aqueous and ethanolic extracts of fresh leaves. Animals pre-treated with aqueous ethanolic extracts shows reduction in enzymatic activities serum bilirubin caused by acetaminophen. The increase in alkaline phosphatase was reduced by almost 50% by aqueous and ethanolic extracts (both 400 mg/Kg, orally for 7 days) whereas the increase in ALT and AST was decreased by more than 70% and serum LDH level was restored. The increase in TBARS was also neutralized by aqueous and ethanolic extracts.10

Devaki and co-workers studied the effect of ethanolic extract of BD on tissue defence system against ethanol induced hepatic injury in rats. The administration of BD extract (150 mg/kg/day for 30 days, orally) reversed the increase in the levels of lipid peroxides and increased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase and reduced glutathione levels.11

Rawat and co-workers reported that the roots of different diameters were collected in three seasons, rainy, summer and winter and examined in thioacetamide intoxicated rats. The results showed that an aqueous extract (2 ml/kg) of roots of diameter 1-3 cm, collected in the month of May (summer), exhibited marked protection of a majority of serum parameters, i.e., GOT, GPT, ACP and ALP but not GLDH and bilirubin, and suggested that the proper size and time of collection of Boerhavia diffusa roots for the most desirable results. Further, the study proved that the aqueous form of drug (2ml/kg) administration has more hepatoprotective activity than the powder form; this is probably due to the better absorption of the liquid form through the intestinal tract. It has been noted in this study that the roots, which were thin, showed maximum protection of serum parameters.12

Chandan and co-workers evaluated the 50% aqueous ethanolic extract of BD whole plant given orally for its hepatoprotective activity in carbon tetrachloride induced hepatotoxicity in rats. The extract significantly decreased the sleeping time from 225 mins to 200 mins induced by CCl4 due to increase in phenobarbitone. It also lowers the SGPT level from 260 𝜇mol/min to 200 𝜇mol/min. It showed reduction of the serum levels of SGPT, SGOT and bilirubin from 270 to 205, 140 to 120, and 1.95 to 1.2 𝜇mol, respectively. It also significantly decreased the increase in prothrombin time induced by CCl4 from 30.43 to 19.01 sec. Also, the bromosulphalein clearance was reduced to 3 times from 16 times by administration of BD extract. It also almost doubles the flow of bile. 13

Figure 1

Mechanism of Hepatoprotection by BDE

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/9092ac12-f2ea-49fc-84e6-68c6d44981d9image1.png

Gulati and co-workers prepared 50% aqueous ethanolic extract of BD roots and evaluated hepatoprotection at a dose of 100 mg/100 g in hepatotoxicity induced by country made liquor. BD extract reduced the increment in serum parameters indicative of damage to the liver. The increase in SGPT, SAP, triglycerides, and total lipid levels was decreased by almost 50% by administration of BD extract while the level of cholesterol was completely restored. SGOT level was not much affected. Histopathological study of the liver showed minimal fatty cysts in BD treated group. The author suggested an additional antilipidemic activity along with hepatoprotective activity. 14

Rajkumari and co-workers also studied that the root extract of the plant have hepatoprotective effect in carbon tetra chloride induced hepatotoxicity in rats, which is evident by modulation in titre of serum alanine aminotransferase (ALT), triglycerides (TG), cholesterol and total lipid. 15

Chakraborti and co-workers studied the hepatoprotective action and it was evident from the reduction in the increased levels of serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) in the treated rats. They also reported that hepatoprotective activity of a steroid androst-5-ene analogue (200 µg/ml) and a flavone 6, 5’-dimethoxy- 5, 7, 3’-trihydroxyflavone (50 µg/ml) isolated from the aerial parts against CCl4 intoxication in in-vitro models.16

Surange and Pendse evidenced that the Ethanol extract of root of Boerhavia diffusa have hepatoprotective effect against country made liquor induced liver toxicity in albino rats, the protective effect of same is evidenced by reduction of elevated alanine aminotransferase (ALT), triglyceride, cholesterol and total lipids in both serum and tissues and the histopathological studies showed that marked reduction in fat deposits in animals receiving Boerhavia diffusa along with country made liquor.17

Table 1

Plant part and type of extract used for the Hepatoprotective activity

Plant part used

Type of extract

Type of Induced toxicity

Activity

References

Fresh leaves

Aqueous Ethanolic

Acetaminophen

↓ enzymatic activities‬‬‬‬‬‬‬‬‬‬‬‬

↓Serum bilirubin

↓ALP, ALT, AST

↓Serum LDL

↓Neutralisation of TBARS

10

Plant extract

Ethanolic

Ethanol induced hepatic injury

↑lipid peroxides

↑superoxide, dismutase, catalase, glutathione peroxidase, glutathione-S-tranferase

↓glutathione levels

11

Root

Aqueous

Thioacetamide

Protection of serum parameters like GOT, GPT, ALP, ALP

12

Whole plant

Aqueous

Carbon tetra chloride

↓sleeping time

↓SGPT, SGOT& Bilirubin

↓prothrombin time ↑flow of bile

13

Whole plant

Aqueous

Country made liquor

↑SGPT, SAP, TG, Total lipid level

↓other serum parameters

14

Root

Aqueous

Carbon tetra chloride

Modulation in titre level of serum ALT, TG, Total lipid, cholesterol

15

Aerial parts

phytochemicals

Carbon tetra chloride

↓SGOT, GPT, ALP

16

plant

Ethanol

Country made liquor

↓ALT, TG, Total lipid, cholesterol

17

Conclusion

As the name affirmed Punarnava (Punar + Nava). Punar means - once again, nava means becoming new, really because of its multiple benefits and pharmacological actions, Punarnava proved itself as magical natural remedy by Ayurveda. Majorly the leaves and the roots are used earlier for the treatment of jaundice, either in the form of raw powder or decoction form. But later when the pharmaceutical era evolved the whole plant from flower to its roots are used for the treatment of diseases. Numerous reports have supported its protective activity on liver diseases. An invitro study conducted on inhibition of crystal growth in liver showed that mixture of magnesium acetate and the herbal extract had effect on inhibiting the growth of crystals when the concentration of herbal extract was increased, when compared to control which had no herbal extract.

Animal studies confirmed that the ethanolic extract of leaves of the plant increased the levels on ALT, AST and decreased the acetaminophen induced toxicity in rats. In other study conducted on ethanol induced hepatic injury showed that the ethanolic extract increased the serum enzymes like superoxide dismutase, catalase etc., and their activities which confirm the protective activity on hepatic injury. 11

 Rawat and others have worked on roots of plant that are collected in different seasons with different sizes and confirmed that the roots collected during summer with thin size had more protection of serum parameters like GOT, GPT, ACP, ALP conducted on thioacetamide induced liver toxicity in rat and showed more protection.12 A study conducted on country made liquor induced toxicity in albino rats showed that increase in ALT, TG, total lipid and cholesterol levels and decreased fat deposits, which reduced the toxicity of liver.17

All these studies showed that the Boerhavia diffusa has protective effect on liver from its diseases. But in vitro tests using laboratory animals and very few clinical studies were available. So, the results obtained may not necessarily be extrapolated to the situation in humans. So further toxicity test on the plant especially during prolonged administration is essential. While there are gaps in the studies conducted so far, which need to be bridged in order to exploit the full medicinal potential of Boerhavia diffusa, it is very clear that this is a plant with tremendous widespread use now and also with extraordinary potential for the future. Further researchers can take up and continue with the human studies since it has been already used in Ayurveda, and several ayurvedic products are in market with regard to kidney, joints and other disease. Pharmaceutical industries can make a great effort in doing animal and human studies and can evolve with the new pharma products.

Conflicts of Interest

All contributing authors declare no conflicts of interest.

Source of Funding

None.

References

1 

C.A. Hiruma-Lima J.S. Gracioso E.J.B. Bighetti L. Germonsén Robineou A.R.M. Souza Brito The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in miceJ Ethnopharmacol2000711-22677410.1016/s0378-8741(00)00178-1

2 

R W Spellenberg Nyctaginaceae Flora of North America Oxford University PressNew York; Date of access2004http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=10617

3 

M L Dhar M Dhawan B N Mehrotra C Ray Screening of Indian Plants for Biological Activity: Part IIndian J Exp Biol1968623247

4 

A R Mahesh H Kumar MK Rangnath Detail study on Boerhavia diffusa plant for its medicinal importance-a reviewRes J Pharm Sci201212836

5 

G. K. Jain N. M. Khanna Punarnavoside: A New Antifibrinolytic Agent from Boerhaavia diffusa Linn.Indian J Chem19892034163610.1002/chin.198934353

6 

S Kadota N Lami Y Tezuka T Kikuchi Constituents of the roots of Boerhaavia diffusa I. Examination of sterols and structures of new rotenoids, boeravinones A and B.Chem Pharm Bull1989371232142010.1248/cpb.37.3214

7 

N Lami S Kadota T Kikuchi Constituents of the Roots of Boerhaavia diffusa L. IV. Isolation and Structure Determination of Boeravinones D, E, and F.Chem Pharm Bull1991391863510.1248/cpb.39.1863

8 

A.N. Misra H.P. Tiwari Constituents of roots of Boerhaavia diffusaPhytochemistry197110123318910.1016/s0031-9422(00)97415-6

9 

S Mishra V Aeri P K Gaur S M Jachak Phytochemical, Therapeutic, and Ethnopharmacological Overview for a Traditionally Important Herb:Boerhavia diffusaLinn.Bio Med Res Int2014201411910.1155/2014/808302

10 

M. Tolulope Olaleye AC Akinmoladun AA Ogunboye AA Akindahunsi Antioxidant activity and hepatoprotective property of leaf extracts of Boerhaavia diffusa Linn against acetaminophen-induced liver damage in ratsFood Chem Toxicol2010488-92200510.1016/j.fct.2010.05.047

11 

T Devaki K Shivashangari S Ravikumar V Govindraju Effect of Boerhaavia diffusa on tissue anti-oxidant defense system during ethanol induced hepatotoxicity in ratsJ Nat Remedies2005521027

12 

A.K.S. Rawat S. Mehrotra S.C. Tripathi U. Shome Hepatoprotective activity of Boerhaavia diffusa L. roots — a popular Indian ethnomedicineJ Ethnopharmacol199756161610.1016/s0378-8741(96)01507-3

13 

B K Chandan A K Sharma KK Anand K K Boerhavia diffusa: a study of its hepatoprotective activityJ Ethnopharmacol1991313299307

14 

R Gulati S Agarwal S S Agarwal Hepatoprotective activity of Boerhaavia diffusa Linn. against country made liquor induced hepatotoxicity in albino rats fed on controlled calorie dietIndian J Pharmacol1991232646

15 

G Rajkumari A Sarala S S Agarwal Hepatoprotective activity of Boerhavia diffusa linn. Against country made liquor induced hepatotoxicity in albino rats fed on controlled calory dietIndian J Pharmacol1991232647

16 

K K Chakraborti S S Handa Antihepatotoxic activity of Boerhaavia diffusaIndian Drugs1989271614

17 

SR Surange GS Pendse Pharmacognostic study of roots of Boerhaavia diffusa Wild. (Punarnava)J Res Indian Med197271



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