Review on Phytochemistry and Pharmacological Aspects of Pedalium murex Linn

 

Ganesh R. Bharskar

Department of Pharmacy, Pravara Rural College of Pharmacy, Pravaranagar.

 

ABSTRACT:

Pedalium murex Linn (belongs to the Pedaliaceae family) commonly referred to as Large Caltrops and Gokhru (India) is a shrub located in the southern part of India's Deccan region, and in parts of Ceylon. The phytochemicals found in the Pedalium murex L. includes ursolic acid, caffeic acid, quercetin, various classes of fatty acid (tritriacontane, tetratriacontanyl riacontanoic acid, nonacosane and heptatriacontan-4-one) and amino acids (tyrosine, threonine, aspartic acid, glycine, histidine and glutamic acid). Phytochemically the P. murex is famous for the containing desirable amounts of diosgenin and vanillin that are considered to be an essential source and useful for the synthesis of steroidal contraceptive drugs and isatin alkaloids as starting material. The Pedalium murex L. have pharmacological activities like antiulcerogenic, antioxidant, nephroprotective, hypolipidemic, aphrodisiac, antibacterial activities. This review is a compilation of knowledge gathered from the research papers published and review the phytochemical and pharmacological aspects of P. murex.

 

 

 

INTRODUCTION:

Pedalium murex Linn is commonly known as Large Caltrops and Gokhru.¹ This species belongs to the family Pedaliaceae, the sesame family. Pedaliaceae family contains 14 genera and 70 species and Pedalium murex is one of them.^1,2 It is a creeper i.e. around 2 to 3 feet long having branches distributed all over, leaves are irregular shape, alternate, repandangulate and in pairs of 5-8 and pedicel with a pair of yellow glands³. Flowers are small and yellow coloured. The fruits are round and have 5 to 12 compartments, each containing one seed. The seeds contain aromatic oil. The roots are 4 to 5 inches long, brown in colour and have a sweet flavour.

 

In the early winters the plant flowers followed by fruiting. P. murex Linn is a succulent herb found near South India's sea coast and some of India's tropical areas. It occurs in the July-September months. It grows luxuriously at temperatures of 25-30℃ in fertile soils and cropland as a weed.⁴

 

ETHNOBOTANY:

Traditionally, Pedalium murex was used in different ways, either as a whole plant or individual plant parts or sometimes in various special preparations. Pharmacologically the P. murex has antiulcerogenic, antioxidant, antibacterial, nephroprotective, hypolipidemic, aphrodisiac and insecticidal activities.¹ It is now considered as a valuable source of specific natural products for formulation of medicines against various diseases and also for the manufacture of industrial products.⁴

 

PHYTOCHEMISTRY:

Extensive phytochemical studies on the plant discovered the presence of various phytoconstituents such as triterpenoids, fatty acids, steroids, vitamins, proteins, sugars, flavonoids, tannins, saponins, vanillin, ursolic acid.¹

 

Chemical constituents:

·       Fruit: Alkaloids (3.5%-5%), stable oil, aromatic oil, resins, glycosides, carbohydrates, saponins and triterpenoids.

·       Stem: Saponins, herman, phytosterols, tannins and carbohydrates.

·       Root: Saponins, Reducing sugars, phenolic compounds, alkaloids, triterpenoids, xanthoproteins and flavonoids.

·       Leaves: Flavonoids, alkaloids, resins, steroids, saponins and proteins.⁵

 

Fruits contain two essential flavonoids including 2’, 4’, 5’-trihydroxy-5, 7-dimethoxy flavones and triacontanyl dotriacontanoate. The research on leaves documented some essential flavonoids including dinatin and 7-glucoronide, diosmetin and its 7-glucoronide, pedaltin and pedalin.⁶ Alkaloids, steroids, resins, saponins and proteins ae also reported. The root contained novel phenolic compounds such as phenol,2-(5,6-dimethyl pyrazinyl) methyl. Saponins, phytosterols, tannins and carbohydrates were reported from stem. Quercetiin, dinatin, querimctrin and an unidentified di glycoside of quercetin were reported from the flower.⁷

 

PHARMACOLOGICAL ACTIVITY:

1.     Antiulcerogenic activity:

Peptic ulcer is caused primarily by lifestyle and dietary changes. Even though a range of drugs are available for the treatment of ulcer, but they produce side effects such as arrhythmias, impotence, gynaecomastia, arthralgia, hypergastrinemia and hematopoietic changes. The use of phytoconstituents as drug therapy to treat major ailments has proved to be clinically effective and relatively less toxic than existing drugs and also reduces the offensive factors serving as a tool in the prevention of peptic ulcer.²⁶ Aqueous extract of leaves of P. murex on ethanol induced gastric lesions at a dose of 200mg/kg, p.o. in a single schedule and 100mg/kg, p.o. Treatment was investigated for 15 to 30 days and was shown to have a significant effect in the treatment of gastric ulceration by evaluating the amount of total acid, acid duration, total protein, ulcer index glutathione, in which famotidine was used as a reference product. Therefore, the aqueous extract of P. murex leaves could be considered as an effective anti-ulcerogenic that could be related to its flavonoid and mucilage content.^8,9 Ulceration was induced in 36 hours fasted rats by the administration of 80% ethanol (1ml/kg) orally. The reference standard (Famotidine, 3ml/100gm) and fresh juice of leaves of Pedalium murex in doses of 0.5, 1.0, 2.0ml/100gm was given to different groups, one hour before the administration of ethanol. A marked gastric mucosal lesion was observed with ethanol. A perceptible elevation in ulcer index, total acidity, acid volume, total protein and elevation of glutathione was observed. Pre-treatment with fresh juice of leaves of Pedalium murex particularly at a dose of 2.0ml/100gm in a single schedule and 1.0ml/100gm for 15 and 30 days treatment annihilated these alterations and elevated the level of glutathione. Therefore, the fresh juice of leaves of Pedalium murex could be regarded as a favourable antiulcerogenic which could be attributed to its content of flavonoids and mucilage.²⁷

 

2.     Anti-dermatophytic:

Dermatophyte infections are very common in India where warm and humid climate and poor hygienic conditions play a significant role in the growth of these fungi. The species Trichophyton and Microsporum form the most widespread etiological agent of dermatophytosis. Several solvent extracts of Pedalium murex L. were screened in the present investigation against two dermatophytes viz., Trichophyton rubrum and Microsporum gypseum. The prominent zone of inhibitions was found at a concentration of 200μg/ml of methanol and petroleum ether extract of Pedalium murex against Microsporum gypseum. The distilled water and methanol extracts of Pedalium murex showed significant activity against Trichophyton rubrum. The standard drugs griseofulvin, fluconazole and ketoconazole were used as the positive control and zones of inhibition were between 10 to 20mm.¹⁰

 

3.     Anti-inflammatory activity:

The maximum phytocompounds were present in hydro alcoholic extracts of P. murex leaf as compared to stem and pod. In vitro anti-inflammatory activity was screened against human red blood cell (HRBC) membrane stabilization method. The maximum percentage of stabilization (82.10±2.93%) was observed at higher concentration of hydro-alcoholic leaf extract. In vitro denaturation of protein was screened by using egg albumin method. The maximum amount of inhibition of protein denaturation was observed in hydro alcoholic extract of stem of P. murex. The above result showed that the hydro alcoholic extract of P. murex possesses anti- inflammatory activity.¹¹ The various parts of Pedalium murex such as root, leaves and seeds are documented to possess different medicinal properties. Animal studies were performed using Carrageenan induced paw edema principle in albino wistar rats. Pedalium murex had shown more anti-inflammatory activity, when compared with Abutilon indium species.¹²

 

 

4.     Antimicrobial activity:

Preliminary phytochemical compounds and antibacterial activity against certain human pathogenic microorganisms is studied for the Petroleum ether, chloroform, acetone and methanolic extract of Pedalium murex L root. The extracts indicated that flavonoids, glycosides, steroids, phenols, alkaloids and tannins were presence. Maximum antibacterial activity in methanolic extract was observed against gram positive bacteria, Streptococcus pyogenes and Enterococcus faecalis than the gram-negative bacteria. The antibacterial activity of methanolic extract of P. murex root was very high in gram positive bacteria at 75% concentration.¹³ A polar solvent Methanol sequestered more variety and amount of phytochemicals than chloroform and hexane. Extracts of Leaf and fruit revealed more variety of compounds than root and stem. Methanolic extracts of all parts of Pedalium murex showed inhibitory action against all the bacteria studied Likewise, methanolic leaf extracts exhibited a low minimum inhibitory concentration accompanied by methanolic stem and root extracts. In between the range of phytochemicals present in the extract and antibacterial activity a direct relationship was observed. Two active compounds dianantin-7-glucoronide and luteolin were active against Pseudomonas putida and Staphylococcus epidermidis was found in Bio-autography studies.¹⁴

 

5.     Antioxidant activity:

Antioxidants have been found to be important in the prevention of human diseases by functioning as free radical scavengers, complexes of pro-oxidant metals, reducing agents and quenchers of singlet oxygen formation.²⁸ The ethyl acetate fraction was found to have high levels of phenolic content (298.72±2.09mg GAE/g). The ethyl acetate fraction exhibit higher total antioxidant capacity, higher % of DPPH radical scavenging activity (135.11±2.95µg/mL), hydrogen peroxide (217.91±6.12 µg/mL), nitric oxide (200.57±4.51µg/mL), deoxyribose (250.01±4.68 µg/mL) and higher reducing power. The Correlation coefficient (r²=0.914) between total phenolic content and total antioxidant activity was found to be significant. The fractions of ethyl acetate are rich in phenolic antioxidants with potent free radical scavenging activity that indicate their value for human health.¹⁵ The in vitro antioxidant activity of aqueous extract of Pedalium murex was investigated for DPPH (1,1-diphenyl-2-picrylhydrazine) scavenging activity and superoxide scavenging activity. Percentage inhibition of free radicals was measured. The antioxidant effects may be correlated with the phenolic acids and micronutrients in the extract. Results clearly indicate that free radical scavenger Pedalium murex is efficient. The aqueous extract of Pedalium murex having moderate superoxide scavenging activity and antioxidant activity is might be due to presence of flavonoids.¹⁶

The experimental model using carbon tetrachloride (CCl₄)-intoxicated rat liver was examined in this research on antioxidant activity of methanol extract of P. murex (MEC) fruits. The hepatotoxic rats were orally administrated with MEC for 90 days (daily, at the dose 70mg/kg bodyweight). Lipid peroxidation in CCl₄-intoxicated rats has been indicated by a marked increase in the levels of reactive thiobarbituric acid and diene conjugates, and also a marked decrease in the amount of glutathione in the liver. These biochemical parameters have reached an almost normal level in CCl₄+MEC-treated rats. The decreased activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in CCl4-intoxicated rats and its recovery to near-normality in CCl₄+MEC-treated rats demonstrated the effectiveness of MEC in the regulation of oxidative stress due to hepatic damage. Elevated level of glutathione transferase shown in hepatotoxic rats also showed signs of a return to normal in co-administration with MEC, supporting the antioxidant efficacy of MEC. The findings provide a rationale for further studies on the isolation of active principles and their pharmacological assessment.¹⁷

 

6.     Hepatoprotective activity:

In the pathogenesis of liver damage, the role of oxidative stress and reactive oxygen species (ROS) generation has been shown. ROS initiate auto oxidation of cell membrane lipids, which lead to cellular necrosis. So, it is well known that they are cytotoxic and involved in etiology of hepatotoxicity. Possibly they reflect the hepatotoxic theory of alcohol and various drugs We evaluated in this study the acute oral toxicity of aqueous-alcoholic extract of P. murex fruits on female Swiss albino mice by AOT 425 guideline. Hepatoprotective activity of aqueous-alcoholic extract of P. murex fruits (200, 400mg/kg) was carried out using alcohol (40% ethanol) and isoniazide induced liver damage in wistar albino female rats. We also measured level of free radical scavenger enzymes (SOD, catalase) in the same models. Aqueous and alcoholic extract of P. murex fruits not showed any mortality up to 5000mg/kg. Significant hepatoprotective activity was observed in alcohol and isoniazide caused liver damage at a dosage of 400mg/kg of aqueous-alcoholic extract. All elevated biochemical liver parameters (SGPT, SGOT, TB, TG and TC) in alcohol- and isoniazide-intoxicated rats dropped by aqueous-alcoholic extract of P. murex fruits considerably close to normal levels. Liver section photomicrograph has also shown hepatoprotective activity. SOD and glutathione levels were significantly increased and lipid peroxidation was significantly reduced with a dosage of 400mg/kg of P. murex aqueous-alcoholic fruit extract. Flavonoids and tannins present in aqueous alcoholic extract can be responsible for hepatoprotective action by scavenging free radicals.⁴

7.     Aphrodisiac activity:

Chronic ethanol exposure has been proposed to cause testicular injury and infertility in males. Petroleum ether extract of Pedalium murex, family Pedaliaceae (PEPM), is examined in this study for its ability to improve aphrodisiac activity and cure germ cell damage induced by ethanol and infertility in male rat models. Doses of 200 and 400mg/kg of PEPM showed a significant increase (P < 0.01, P < 0.001) in mating and mounting behaviour. In comparison with the ethanol-treated group the impact on fertility variables such as total body weight, percentage of pregnancy litter size has also increased significantly (P < 0.01). In PEPM-treated groups significant increases in sperm motility and count were observed in a dose-dependent manner (P < 0.01; P < 0.001) as compared to the ethanol-treated group. Similarly, decreases in the concentration of defective sperm have been observed in 400mg/kg PEPM-treated animals. The effects of PEPM on total protein, total cholesterol and testosterone were satisfactory, the levels being increased significantly for protein (P < 0.05), cholesterol (P < 0.01) and testosterone (P < 0.05) by 400 mg/kg PEPM. Microtome sections of animal tests treated with 400mg/kg PEPM demonstrated the regeneration and recovery of germ cells and luminal spermatozoa and were comparable with the animals of the control group. Such PEPM effects make this natural herb ideally suited as an aphrodisiac and a potent fertility-enhancing drug.¹⁸ Pedalium murex ethanolic extract with a dosage of 125, 250, and 500mg/kg p.o. administered to rats followed by 2g/kg p.o. of glucose 30 min after the administration of extract. In the treated groups pregnancy was detected after 20-25 days of treatment in females resulting in the birth of pubs ranging up to ten in some females (more significant in the case of 500mg/kg p.o.). The study also revealed a significant rise in pub weights along with a regular pattern of behaviour. The increased rate of pregnancy in the groups treated with the drug may be attributed to healthy viable sperm and enhancement of rat sexual desire. From this it can be inferred that plant fruits can be used as a great aphrodisiac agent to promote fertility rate.¹⁹

 

8.     Anti hyperlipidaemic activity:

Anti-hyperlipidaemic potential of the ethanolic extract from Pedalium murex fruits at doses of 200 and 400 mg/kg/p.o. studied in rats supplemented with high fat diet. Biochemical parameters such as serum total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglycerides (TG) levels were assessed and contrasted with animals treated concurrently with the Gemfibrozil and Atorvastatin as reference standards. The ethanolic extract showed a significant decrease in triglycerides (p<0.01), LDL (p<0.001), VLDL (p<0.01), cholesterol (p<0.001) and significant increase in HDL (p<0.05) levels at the tested doses. The studies conducted by comparing with standard drug treated group (Gemfibrozil and Atorvastatin).²⁰

 

9.     Antiurolithiatic activity:

Most calculi in the urinary system arise from a common component of urine, calcium oxalate (CaO), representing up to 80% of analyzed stones.³¹ Pedalium murex L. is a traditional herb widely used to treat problems associated with the kidney stone. Struvite stone can swiftly grow and become ‘staghorn calculi’ in kidney and its associated areas, which is the most aching urological disorder. The present study examined anti-urolithiasis activity of ethyl acetate extract of P. murex L. (EAEP) against struvite crystal. The antibacterial activity of ethyl acetate extract of P. murex L. investigated against various urease producing bacteria. It indicated the minimum bactericidal concentration (MBC) (> 125) against the Escherichia coli and Staphylococcus aureus. On the other side, total mass, volume, number, rate of growth and dissolution of synthesized struvite crystals were observed at various concentrations of 0.5%, 0.75%, 1% of EAEP and without EAEP. In which, EAEP addition showed significantly reduced struvite crystal. Alternatively, MgO (300mg of EAEP/kg/body weight) induced urolithiasis of Wistar albino rat at the rate of 1 ml for 28 days. Various biochemical parameters in serum, urine and histological analysis of kidney were taken for evaluation. Significant results (p < 0.05) were observed in 1% EAEP (300mg) treated group than cystone treated group. From the histological study, reduced renal damage and glomerular development were observed. Our experiment, P. murex L. enhances the reducing activity on struvite crystal and prevents in-vitro and in- vivo the crystal formation. It can be suggesting that P. murex L. and its phytocomponents could be used as treatment for the management of kidney stone by dissolving the struvite stone in kidney.^21,22

 

Pedalium murex showed significant improvement in renal function and kidney weight in prophylactic groups as compared to ethylene glycol controls. It doesn’t affect on urinary oxalate, urine volume and any other serological parameters. Calcium oxalate crystallization was significantly decreased in all the Pedalium murex treated groups. Calcium oxalate and phosphate mineralization were also inhibited by 33% and 57%. Ethanolic extract of Pedalium murex fruits possess significant activity for prevention of renal calculi.²³

 

10. Nephroprotective activity:

Cisplatin is a potent anti-tumour drug, but its clinical use is limited due to its renal toxicity. Many pharmacological trials documented beneficial effects of certain Indian Medicinal plants to protect against kidney and renal damage. The ethanol extract of dried fruits of Pedalium murex for nephroprotective activity in Cisplatin causing renal damage to rats is investigated here. The intraperitoneal administration of Cisplatin 5mg /kg caused nephrotoxicity in Wistar rats. The Effect of concurrent oral administration of Pedalium murex ethanolic extract was determined at a dose of 250mg/kg using serum creatinine and blood urea and change in body weight as indicators of kidney damage and Cystone was used as standard drug. The extract significantly reduced the cisplatin induced nephrotoxicity. Notable improvements in body weight, plasma creatinine, and urea levels were observed. The ethanolic extract has been found to effectively protect the kidneys from damage. Current studies show that the ethanolic extract of Pedalium murex dried fruit is a potent nephroprotective compared to cystone.²⁴

 

11. Antipyretic Activity:

The aqueous and ethanolic extracts of Pedalium murex was investigated using Brewer’s yeast-induced pyrexia models for antipyretic activity in rats. Brewer’s yeast (15%) was used to induce pyrexia in rats. Both the extract (200 and 400mg/kg body weight p.o produced a significant (p<0.05) dose dependent inhibition of temperature elevation compared with the standard drug Paracetamol (150mg/kg body weight). The aqueous extract significantly (P<0.001) reduced yeast induced pyrexia in rats at doses of 200mg/kg b.w. These results indicate that leaf extracts of Pedalium murex possesses potent antipyretic effects and thus pharmacologically justifying its folkloric use in the management of fever.²⁵

 

12. Anthelmintic activity:

The roots of plant were extracted with petroleum ether and ethanol. The anthelmintic activity of these extracts was screened by taking Indian earthworm (Pheretima posthuma) as a test organism and albendazole and piperazine citrate were used as reference standards. All the extracts show significant anthelmintic activity. It is concluded that Pedalium murex roots shows significant anthelmintic activity.²⁹

 

13. Neuroprotective activity:

EEPM showed significant results in preliminary phytochemical studies and in vitro free radical scavenging activity prompted us to select the ethanol extract for pharmacological screening. In this study, results of behavioural tests for anxiety and depression, agitated levels of in vivo non- enzymatic and enzymatic anti-oxidant parameters indicated that the endotoxin, LPS, lead to anxiety, depressive like behaviour in rats, which were found to be reversed by EEPM when compared to control treated groups. These results indicated that EEPM may be a potential candidate for LPS-induced brain damage which may be attributed to the presence of potent antioxidants in EEPM. Such new findings may be included as strategies for more effective neuroprotection in addition to current therapies.³⁰

 

CONCLUSION:

P. murex is a valuable source of medicinally beneficial compounds commonly used for various ailments. In various research leaf and fruit extracts from this plant showed good source for the bioactive compounds. Therefore, plants studied here can be a potential source of useful drugs, if they are involved in further research. Scientific research on P. murex indicates this plant has significant biological potential.

 

CONFLICT OF INTEREST:

The authors report no conflict of interest.

 

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