INTRODUCTION:

The natural products, especially those derived from plants, have been used to help mankind sustain human health since the dawn of medicine. The traditional medicine has been used since time immemorial and has been well accepted and utilized by the people throughout history. Since ancient times, plants have been an excellent source of medicines¹. Plant-derived medicinal products have attracted the attention of scientists around the world for many years due to their minimum side effects and positive effects on human health^2,3. The Psoralea corylifolia L. family is Fabaceae (Leguminosae), and is an endangered herbaceous and medicinally useful plant. It is mostly found in tropical and subtropical region of the world and it grows in the plains of Central and Eastern India^4,5.

The Psoralea corylifolia has enormous uses as it is an important component of ayurvedic as well as allopathic system of medicine and it is mostly used in the treatment of various skin diseases like, psoriasis, leucoderma and in many medicinal formulations^6,7. Through Ayurvedic literature the properties of Bakuchi plant is documented as the Sanskrit shloka states the use of Bakuchi in various Ayurvedic treatments as in skin disorders, skin and hair treatments, as a germicidal, Bronchial Asthama and Cough, Anaemia and Oedema. The plant showed some of activity like antibacterial, antifunga, antioxidant, anti-inflammatory, antiflarial, estrogenic, antitumour, and immunomodulatory activity⁸. In Ayurvedic system of medicine in some skin diseases and disorders such as psoriasis, vitiligo leucoderma and leprosy in the form of internal as well as external applications and it is used in the treatment of eczema and hair loss^9,10. The plant roots are useful in dental caries, fruits are laxative, aphrodisiac, and are used for the treatment of leucoderma, leprosy and in inflammatory diseases of the skin and leaves are good for the treatment of diarrhoea^11,12.

Classification:

The plant classification details are:¹³

Kingdom: Plantae

Division: Angiospermae

Class: Dicotyledoneae

Order: Rosales

Family: Leguminosae

Subfamily: Papilionaceae

Genus: Psoralea

Species: corylifolia Linn.

Description of the Plant:

It is a small, erect, annual herb growing up to 60–120cm in height throughout sandy, loamy plains of Central and East India^15,16. The seeds contain an essential oil (0.05%), a non volatile terpenoid oil, a dark brown resin (8.6%), and traces of alkaloidal substance.

Chemical composition of the plant:

The plant contain various chemical compounds including flavonoids (neobavaisoflavone, isobavachalcone, bavachalcone, bavachinin, bavachin, corylin, corylifol, corylifolin and 6-prenylnaringenin), coumarins (psoralidin, psoralen, isopsoralen and angelicin) and meroterpenes (bakuchiol and 3-hydroxybakuchiol)¹⁸. Very high concentrations genistein found in the leaves of Psoralea corylifolia¹⁹. Many studies have confirmed that plants and foods rich in polyphenolic content are effective scavengers of free radicals, thus helping in the prevention of these diseases through their antioxidant activity²⁰. Antioxidants which are present in plants, herbs and dietary sources help in preventing vascular diseases in diabetic patients²¹. The tannins and flavonoids are the secondary metabolites in plants supposed to be the natural source of antioxidants which stop destruction of β-cells and diabetes-induced ROS formation²² it is used to manage diabetes as a whole with plants which show good enzyme inhibitory and antioxidant activities²³.

Traditionally uses:

The seed oil is mostly beneficial, externally in numerous skin ailments. For hypo pigmented lesions if the skin likes leucoderma and psoriasis respond well, to local application along with oral therapy. The seed powder mixed with (Yellow arsenic), in 4:1 proportion and mashed with the cow`s urine for leucoderma treatment. This paste is applied on the lesions of leucoderma²⁵. The bakuchi seed powder mixed with buttermilk is applied externally for scabies and ringworm infection treatment. For leprosy, the seed oil is recommended orally, with beatlenut leaf²⁴. The bakuchi and karanji oil used in chronic skin with Vaseline, Scabies, Psoriasis ringworm and tinea versicular are treated successfully with bakuchi ²⁶.

Plant parts and their uses:

The plant used both externally internally. Most parts of the plant (roots, leaves, seeds and an oil from the seeds) less to be used, seeds being most commonly used.

Seed:

Seed and extract powder are used as diuretic, anthelminthic, laxative, and for healing wounds^13,14. Seeds are antipyretic and alexiteric²⁸. Seeds are used as stomachic, stimulant, aphrodisiac, and diaphoretic²⁹. It is an effective against impotence, menstruation disorder, and uterine hemorrhage. It shows coronary vasodilatory activity It is a cure for gynecologic bleeding. It is also used to treat spermatorrhea and premature ejaculation.

Roots:

The root of the plant is useful in treating the caries of the teeth. Psoralea corylifolia is used to promote bone calcification, making it useful for treating osteoporosis and bone fractures³². The root of the Psoralea corylifolia plant used in the treatment of dental problems.

Leaves:

Leaves are used to alleviate diarrhea³².

Fruits:

Fruit is bitter, helps to prevent vomiting, cures difficulty in micturition, used in treating piles, bronchitis, and anemias and improves complexion³⁵. The fruit of the Psoralea corylifolia plant have properties aphrodisiac and applied to the genital organs, as a tonic. The fruits used for treating febrile diseases, incontinence, premature ejaculation, bed wetting, frequent urination, impotence and lower backaches.

Oil:

The use of Psoralea corylifolia oil help to cure several skin diseases like tinea versicular, scabies, ringworm and psoriasis. The babchi oil use for vitiligo treatment.

Other uses:

Seeds are used to make perfumed oil³³. The ethanolic extract has been used as a food additive for the preservation of some processed foods or pickles. The cake of seeds rich in nitrogen and minerals is used as feed or manure.

Pharmacological activities:

Many investigations have been conducted on the pharmacological properties of the P. corylifolia and which are mentioned below.

Antibacterial activity:

From the seeds the three new prenyiflavonoids, namely corylifols A-C (1-3), were isolated fom P. corylifolia and which showed antibacterial activity against Staphylococcus aureus and S. epidermidis³⁴.

Anti-psoriatic activity:

Babchi seeds powder (Safoof) were found effective in the treatment of (psoriasis) at the dose of 6gm in the form of (infusion) twice a day on empty stomach for 45 days in 40 patients. Other trial showed that Psoralia corylifolia seed extract had potential antipsoriatic activity. Other trial showed that the use of psoralen along with its chemical derivatives, namely, trioxalen, supplemented with exposure to sunlight is a more effective treatment for psoriasis^38,39.

Antitumor activity:

The activity-oriented fractionataion of Psoralea corylifolia led to and isolation of a (+) bakuchil 1 as an active principle of its antitumoral property in vitro. It showed that it exhibit a mild cytotoxicity against five kinds of cultured human cancer cell lines. I.e. the A549, SK-OV-3, SKMEL-2, XF498 and HCT-15. The synthesized 2,3 epoxide of bakuchiol showed the similar activity as the bakuchiol. Whereas the other oxidation derivatives 4 and 5 including the acetyl (+) bakuchiol 2 showed a decreased activity⁹.

Pesticidal activity:

From chloroform extract the pure compound 6-(3-methyl but -2-enyl) 6-7 dihydroxycoumestan 1 isolated from the seed of P. corylifolia L. was showed the pesticidal activity against both adults and different instars of Tribolium casteneum Hebrst.^28,44.

Anti-Inflammatory Activity:

From the fruits bavachini an isolated which revealed a marked antiinflammatory, antipyretic, and mild analgesic properties at a dose of 25–100mg/kg? It has demonstrated better antipyretic activity than paracetamol and showed no effect on the central nervous system, and the maximum lethal dose was greater than 1000mg/kg in mice. Several flavonoids from P. corylifolia might be useful remedies for treating inflammatory diseases by inhibiting IL-6-induced STAT3 activation and phosphorylation. It also showed antiinflammatory activity against carrageenan-induced edema in rats⁴¹.

Estrogenic Actvity and Bone Density:

Estrogenic activities of ethanol extract and its active components from P. corylifolia L. were studied using various in vitro assays. The ethanol extract from the component were analyzed to be bakuchiol, psoralen, isobavachalcone, isobavachromene, and bavachinin. In a fractionation procedure, hexane and chloroform fractions showed estrogenic activity in yeast transactivation assay and Escreen assay. The ethanol extract, hexane, and chloroform fractions showed significantly higher activities at a concentration of 1.0ng/ml, and bakuchiol at the concentration of 10 6 M was showed the highest activity, especially, which was higher than genistein at the same concentration in yeast transactivation assay, In E-screen assay, cell proliferation of bakuchiol (10 6 M) showed similar estrogenic activity with genistein (10 6 M). In ER binding assay, bakuchiol displayed the strongest ER-binding affinity (IC50 for ERα = 1.01 × 10 6 M, IC50 for ERβ = 1.20 × 10 6 M) and bakuchiol showed five times higher affinity for ERα than for ERβ ³¹.

Antioxidant Activity:

In antioxidant activity the structures of the isolated compounds were identified by (1) H NMR and (13) C NMR. The antioxidant activity estimation by electron spin resonance (ESR) method showed that psoralidin was the most active antioxidant with an IC50 value of 44.7microM. The powder and extracted plant showed the strong antioxidant properties when tested in lard at 100°C by using oxidative stability instrument. The antioxidant activity of compounds decrease in the following order: Psoralidin > BHT > α-tocopherol > bakuchiol > corylifolin > corylin > isopsoralen > psoralen. Bakuchiol and 2 of the flavonoids, isobavachin and isobavachalcone, showed broad antioxidant activities in rat liver microsomes and mitochondria^4,20.

Anti -helminthic Effect:

The alcoholic extracts of seeds of evaluated for antihelmintic activity using two-enzyme system taking rat brain as a model for Ascaridia galli^50,43.

Anti-fungal Activity:

It is demonstrated that the methanol seed extract of Psoralea corylifolia show antifungal activity against M. furfur, C. albicans, and A. niger as compare to seed oil⁴⁴.

Antidiabetic activity:

P. corylifolia showed the anti-hyperglycemic and antioxidant activity^21,22,23. The trial found that the ethanolic extract of seeds of Psoralea corylifolia in streptozatocin (STZ) nicotinamide induced type 2 – diabetic rats.

DNA Damage protection activity:

The ethanol, methanol and water extracts of Psoralea corylifolia showed significant antioxidant potency compared to other solvent extracts and also possess metal chelation and protection against DNA damage and possess antibacterial activity. Hence it suggested that seeds of Psoralea corylifolia have potential application in food systems as an antioxidant and probably in biological systems as a nutraceutica⁴⁶.

DNA polymerase and topoisomerase II inhibitors:

In DNA polymerase inhibition an ethanolic extracts of seed cause the strong inhibition in a whole cell bioassay specific for inhibitors of DNA replication enzymes. The two new compounds isolated me, e corylifolin 1 and the known compounds led to the isolation of the new compound bakuchiol 2 as DNA polymerase inhibitors^{47, 25}.

Anti-AIDS activity:

This plant also used against treatment of AIDS. Psoralen and Isopsoralen, the main active compounds isolated from Psoralea corylifolia are being investigated against AIDS⁴⁸.

Antipsoriasis:

The ethanol seed extracts exhibited or showed the effect of anti-psoriatic and anti-bacterial activity. The extracts of seeds showed s effect on psoriasis which was concluded by measuring mean thickness of epidermis and histopathological reports and anti-bacterial studies by zones of inhibition and MIC^38,39.

Hepatoprotective activity:

From the aqueous extract of seed of P. corylifolia possess the one hepatoprotective compound, bakuchiol 1, together with two moderately active compounds, bakuchicin 2 and psoralen 3, on tacrine-induced cytotoxicity in human liver- derived Hep G-2 cells⁵⁰.

Osteoblastic proliferation:

The fruit extracts exhibited osteoblastic proliferation stimulating activity in UMR 106 cell line cultured in vitro. The corylin and bavachin flavonoids were isolated and identified as active principles by activity-guided fractionation. The corylin and bavachin from fruits extract might stimulate bone formation of have potential activity against osteoporosis³².

Neuroprotective Activity:

It is demonstrated that Psoralea corylifolia Linn seed extracts showed the significant protective effect against 3-nitropropionic acid induced cytotoxicity. Thus, P. corylifolia Linn seed extracts may have potential applications as therapeutic agents for treating neurodegenerative disease⁵².

Reproductive Toxicity:

P. corylifolia an ethanolic extract at 0.375, 0.75, 1.5, or 3% of the rat diet by weight for 90 days noted decreases in weight at doses of 0.75% and above accompanied by decreased gonad weight (testes and ovaries) at doses of 1.5-3% of the diet. As a previous study on 8-methoxypsoralen was accompanied by testicular atrophy, (National Toxicology Program report 1989) it was thought that these doses were showing Psoralen-induced reproductive toxicity. Increased yGPT and BUN were also noted at the highest dose (3%) in both sexes, and also at 0.75-1.5% in female rats. The study in rats suggested that 8g/kg bodyweight Psoralea (estimated human dose of 87g for a 150lb female) could potentially be associated with reproductive toxicity in female pregnant rats⁵³.

Anti-Depressant Activity:

The various studies in rats suggesting a possible anti-stress and anti-depressant effect, although they are not to a remarkable degree. TFPC possess potent and rapid antidepressant properties that are mediated via MAO, the hypothalamic–pituitary–adrenal axis, and oxidative symptoms. P. corylifolia, is most potent and valuable drug for the treatment of depression in the elderly. also proved psoralen's antidepressant effects, using forced swimming test model of depression in male micsed, and there is possibility of interactions between Psoralea and classical stimulant⁵⁴.

Antiviral activity:

P. corylifolia crude ethanolic extract of the seeds was revealed to have high activity against the severe acute respiratory syndrome corona virus (SARS‐CoV) papain‐like protease (PLpro) with an IC 50 of value of 15 μg/ml. SARS‐CoV‐PL pro is a main enzyme that has a vital role in SARS virus replication⁵⁵.

Antiprotozoal activity:

The extract of P. coryfolia with methanol showed excellent activity against I. multifiliis theronts in concentration of 1.25mg/L or more when was revealed for a period of 4 hr. The Psoralea corylifolia extract at 5.00mg/L concentration produce 100% mortality of protomonts and 88.9% of encysted tomonts. It was found that longer time (24hr) and more concentration (5.00 mg/L) caused the significant reduction of the survival rate and reproduction of tomont of I. multifiliis, which were exited from the fish after in‐bath handling in situ (Ling et al., 2013). Psoralea corylifolia has been found to be an alternative to malachite green to control I. multifiliis, an external protozoan parasite. The screening showed that Psoralea corylifolia extract have the more activite against I. multifiliis theronts. When the experiments were conducted in vivo, at 1.25mg/L or more concentrations of methanol extract of P. corylifolia, it caused 00% mortality of theronts during the 4 hr of exposure^38,39. This study showed the damaging effect of P. corylifolia against I. multifiliis trophont in situate same study leads to the evaluation of the activity of antiprotozoal compounds extracted form P. corylifolia against I. multifiliis.

Anti‐Alzheimer's:

The two compounds isolated from commonly used in clinical practices in ancient Chinese Medicine P. corylifolia named as IBC and BCN mod-late amyloid β(Aβ) peptides, especially the peptides with 40 (Aβ40) or42 (Aβ42) residues, which are believed to be responsible for the development of amyloid plaques in Alzheimer's disease. The peptides prepared in the lab in dried form in DMSO; Aβ42 5mg/ml was used and was diluted in PBS to 50μM. Both the compounds acted in variuos way. IBC importantly inhibits both oligomerization and fibrillarization of Aβ42, whereas BCN converts Aβ42 into large unstructured build up in neuroblastoma cells. Both compounds were quite effective in Alzheimer's^51,52.

Anti‐obesity:

The various studies on animals exposed that genistein has the ability to reduce the body weight by reducing food intake. It also reduced theft pad weight and enhanced the apoptosis of adipose tissues. For example, one such study was performed on ovariectomised mice. This commonly known trihydroxyflavone, Genistein, has also been isolated from P. corylifolia, exhibited a potential anti‐obesity and obesity related low grade inflammation activities through multiple mechanisms and cell signalling pathways. P. corylifolia extract possesses anti‐obesity and ant‐diabetic activity by its action on adipocyte life cycle, obesity‐related low‐grade inflammation, and oxidative stress^58,48.

Anti‐coagulant effect against snake venom:

P. corylifolia extract neutralized the coagulation of caused by Naja naja karachiensis snakebite when compared with the antidote used as a standard. The snake venom was experimented on humanplasma (citrated) to evaluate its effect on activated partial thromboplastic time (aPTT), prothrombin time (PT), and thrombin time (TT). Snake venom (200μg/ml) was found to delay PT (13±0.57 to 23±0.57 sec), aPTT (35±1.52 to 48±2.0 sec), and TT (13±0.57 to 33±0.57 sec). PT and TT were prolonged, and it suggested the occurrence of thrombin‐like or plasminogen activating enzymes⁵⁹.

Immunomodulatory activity:

The extract of seeds of P. corylifolia has been showed to have stimulant activity against natural killer cells when tested in mice. This study showed that the extract also modulates the antibody dependent cellular toxicity. On the time tumour development, the seed extract also inhibited the antibody complement mediated cytotoxicity. The study was conducted on Balb/cmale mice. The dose of 100mg/kg was administered intra-peritoneal. The blood collected from punctured heart and serum was separated to study the antibody complement‐mediated cytotoxicity. The natural killer cells were removed from spleen, and antibody‐dependent cellular cytotoxicity was assessed^60,9.

Lymphangiogenisis inhibition:

The extract of Psoraleae and the bioactivity guided fractioned com-pounds, including psoralen, p‐hydroxybenzaldehyde, psoracorylifol D, angelicin, BCN, isobavachalone, and bakuchiol hydroxybakuchiol, caused significant inhibition (in vitro) of the proliferation of temperature‐sensitive rat lymphatic endothelial (TR‐LE) cells. Among isolatedcompounds, psoracorylifol D, isobavachalone, BCN, hydroxybakuchiol, and bakuchiol inhibited proliferation and the formation of the capillary‐like tube of TR‐LE cells. In the Tube formation assay to analyze the cellcycle of the TR‐LE cells, the concentration of 10μm of bakuchiol wasused and incubated for 6–48 hr. After reaping, the propidium iodide was used for staining. Other compounds tested showed selectiveactivity. The compounds tested might be good candidates for development of anti‐neoplastic and anti‐metastatic agents against lymphangiogenesis⁶¹.

Negative Effects:

The potential hepatotoxicity of herbal remedies is usually ignored in daily life. P. corylifolia appeared to be associated with the occurrence of acute cholestatic hepatic injury. Some alternative medicine therapists claim that P. corylifolia is effective for the treatment of osteoporosis. They observed a case of acute cholestatic hepatitis associated with the use of the seeds of P. corylifolia in quantity over 10 times the usual dose in a postmenopausal woman. Liver biopsy showed zone three necrosis, degenerating cells, cholestasis, and infiltrations with inflammatory cells. This case stresses the need to warn of the potential hepatotoxicity of the seed of P. corylifolia, especially in a large dose⁶².

Industrial application of isolated compounds:

Several compounds isolated from Psoralea corylifolia have many industrial uses and are available commercially. A few examples which are as an following: the compound Angelicin (CAS 523‐50‐2) is available as antifungal compound. The methoxsalen (8‐Methoxypsoralen; CAS 298‐81‐7) are called as a potent suicide inhibitor of cytochrome P‐450. The bakuchiol (CAS 10309‐37‐2) is available as a PTP1B and DNA polymerase inhibitor Bavachin (CAS 19879‐32‐4) is available as weak antioxidant that stimulates bone formation. The compound Daidzin (CAS 552‐66‐9) isolated from different plant species is a potent inhibitor of human mitochondrial aldehyde dehydrogenase that demon-states chemo preventative activities. The com-pound Genistein (CAS 446‐72‐0) is available as a highly specific inhibitor of protein tyrosine kinase. These examples clearly focused on importance of bioactive compounds isolated from P. corylifolia, important traditional medicinal plants^62,63.

CONCLUSION:

The plant used as medicinal agent since, ancient time. The popularity of traditional medicinal plants or their derivatives prevention and management is increasing worldwide. The extensive survey of literature revealed that P. corylifolia is an important traditional medicinal properties with array of pharmacological activities. The clinical- based studies confirmed that it play an important role in the prevention and management of various diseases.

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Received on 19.02.2021 Modified on 03.05.2021

Asian Journal of Pharmacy and Technology. 2021; 11(3):238-244.

DOI: 10.52711/2231-5713.2021.00039