Available online on 15.01.2022 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2022 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                        Review Article 

Abrus precatorius: A comprehensive insight into the phytochemical, pharmacological, therapeutic activities, and safety

Aswin Rafif Khairullah¹ , Tridiganita Intan Solikhah²* , Arif Nur Muhammad Ansori¹ ,    Gavrila Amadea Puspitarani³ , Dina Dewi Anggraini⁴ , Gabrielle Ann Villar Posa⁵ 

¹ Doctoral Program in Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia 

² Division of Veterinary Clinic, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

³ Infectious Diseases and One Health, Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh

⁴ Midwifery Study Program, Poltekkes Kemenkes Semarang, Semarang, Indonesia

⁵ School of Environmental Science and Management, University of the Philippines Los Banos, Los Banos, Philipines

Introduction

                  Since the beginning of human civilization, herbal plants have often been used to cure various diseases ^1–3. Herbal plants have been an ancient tradition much older than contemporary pharmacology, medicine, and chemistry ^4,5. The World Health Organization reported that around 75% of the world's population still uses medicinal methods derived from herbal plants ⁶. In addition, medicines from herbal plants are widely used because they are cheaper, safer, and have various pharmacological activities ^7–9.

A. precatorius, a plant belonging to the Fabaceae family, has good potential to be used as herbal medicine ¹⁰. This plant is commonly known as Indian licorice, Crab's eye, Jequirity, and Rosary pea. This plant is known as Gunja in Sanskrit and Ratti in Hindi ¹¹. A. precatorius is native to India; however, it can be found in all tropical and sub-tropical regions around the world ¹².

A. precatorius was first described as a medicinal plant by William Boericke in the Homoeopathic Materia Medica entitled Jequirity ¹³. This plant is traditionally used to treat cuts, wounds from animal bites, and several other diseases such as rabies, tetanus, and leucoderma ¹⁴. This plant is also effective in treating dysentery and diarrhea ¹⁵. In addition, this plant also shows efficacy as a tonic, aphrodisiac, emetic, and laxative ¹¹. A. precatorius is believed to have various pharmacological activities such as antibacterial, antihelminthic, antidiabetic, and antitumor ¹³.

Given the efficacious of the A. precatorius plant as a medicinal plant, this review offers a comprehensive insight into the phytochemical, pharmacological, therapeutic activities, and safety of A. precatorius, and demonstrates that it can be used as a reliable source for preparation of new drugs.

Origin Names

This plant in Indonesia is called Saga or Weglis; in Philippines Jequirity; in Nepal Rati gedi or Crab's eye; in Egypt Rosary pea; in Pakistan Gunchi; in USA Precatory bean ¹⁰.

Taxonomy

Kingdom: Plantae 

Division: Magnoliophyta 

Class: Magnoliopsida 

Order: Fabales 

Family: Fabaceae 

Genus: Abrus 

Species: Abrus precatorius L. ¹⁶

Plant description

A. precatorius is a twisted woody vine capable of growing up to 6 meters. The leaves resemble feathers, compound, alternate, pinnate with small oval leaflets. The branches are greenish-yellow. The flowers are abundant and appear in the leaf axils along the stem. The flowers are small and clustered with a length of 3 cm to 8 cm. The flowers are white or purple. The fruits have a nut-like shape with a length of about 3 cm containing hard ovoid shiny seed in black, dark red, with a length of about 1 cm. The seeds are red with a black spot covering one end. The roots are tortuous and branched ¹⁷. The morphology of A. precatorius can be seen in Figure 1.

Figure 1: Abrus precatorius L. ¹⁸

Geographical distribution

A. precatorius grows in tropical and subtropical areas of the world. The plant can be found in China, India, South Africa, and Brazil, and commonly found throughout the plains of India, from the Himalayas to South India and Ceylon. This plant is able to grow at an altitude of 1200 m in the Himalayas ¹¹. In addition, it is also widely cultivated in Nigeria and Southeast Asian countries ¹⁹.

Phytocemistry

The phytochemical content of the parts of A. precatorius plant are as follows:

Leaves

A. precatorius leaves contain pinitol, triterpene glycosides, glycyrrhizin up to 10%, and alkaloids such as hepaphotine, precatorine, abrine, choline ¹¹. Triterpene glycosides consist of abusosides A, B, C, and tree glycosides based on abrutigenin and cycloartane type aglycones ²⁰. Other active compounds found in A. precatorius leaves are abruslactone A, tritepenes abrusgenic acid, methyl abrusgenate, liquirtiginin-7-diglycosides, liquirtiginin-7-monoglycosides, toxifolin-3-glucoside, and the flavonoid vitexin ²¹.

Seeds

A. precatorius seeds contain carbohydrates (42.42%), fat (3.92%), ash (5.38%), moisture (5.06%), crude protein (39.20%), and crude fiber (9.08%) ²². The active compounds found in the seeds of A. precatorius are flavonoids, steroids, alkaloids, anthocyanins, lectins, and fixed oils ²³. Alkaloids from the seeds of A. precatorius contain choline, hepaphotine, precatorine, and abrine ¹¹. A. precatorius seed oil contains a lot of linoleic acid and oleic acid ²⁴. Steroids from the seeds of A. precatorius contain stigmasterol, -sitosterol, abricin, 5β-cholanic acid, cholesterol, and linoleic ²⁵. The red color of A. precatorius seeds is due to the presence of pelargonidin, delphinidin, abranin glycosides, and cyanide ²⁶. Several other compounds such as sophoradiol, sapogenol, hederagenin methyl ether, abrisapogenol J, kaikasaponin III methyl ester, flavones such as aknone and abrectorin are other major constituents of A. precatorius seeds ²⁷. The main constituents of A. precatorius seeds are lectins and abrins. Lectins are toxic (abrin) and non-toxic (abrus agglutinin). Abrin is denoted by abrin a, b, c, and d consisting a large β-polypeptide chain and a short polypeptide chain linked by disulfide bonds ²⁸.

Root

The roots of A. precatorius contain glycyrrhizin compounds and alkaloids such as precasine and abrasives in addition to abrine and related bases ²⁹.

Medicinal benefits

The medical benefits of parts of the A. precatorius plant are as follows:

Leaves

The leaves of A. precatorius can be used as a tonic and aphrodisiac. The leaves of A. precatorius can also be used to treat leucoderma, skin diseases, itching, eye diseases, and wounds ²⁶. In addition, the leaves of A. precatorius are also efficacious to treat stomatitis, asthma, dental caries, migraine, fever, and tuberculosis ³⁰. A. precatorius leaves soaked in warm oil are applied to the surface of the skin, experiencing rheumatic pain ²⁶. A. precatorius leaves juice mixed with oil can be applied over a bloating stomach ³¹. A. precatorius leaves powder mixed with sugar are used to treat menorrhagia and leucoderma ³². A. precatorius leaves can also be used to treat gastritis, diarrhea, insomnia, cancer, kidney disease, and heart disease ³³.

Seeds

A. precatorius seeds can be used to treat skin diseases, ulcers, and nervous system disorders ³⁴. A. precatorius seeds that are processed into a paste can be applied to the skin to treat shoulder joint stiffness, sciatica, bruises, and paralysis ³⁵. Seeds of A. precatorius can be used as a laxative, but it should be noted that in large doses, it will be toxic and cause cholera-like symptoms ³⁶. A. precatorius seeds can also be used as a natural contraceptive ³⁷. 

Root

A. precatorius roots can be used to treat rheumatism, alexiteria, laryngitis, and vomiting ³⁸. A. precatorius root extract can be used to treat coughs ¹⁰. In addition, the root can also be used to treat cancer, gastritis, diarrhea, insomnia, kidney disease, and heart disease ³⁹. A. precatorius roots has its own uses in treating jaundice, gonorrhea, and other infections ³².

Traditional uses

A. precatorius has anti-suppurative properties; the A. precatorius plant ground with lime can be used to treat acne and abscesses ¹⁰. Oral decoction of A. precatorius leaves can cure colds and coughs ²⁶. The root of A. precatorius is useful for treating hemoglobinuric bile and jaundice ¹¹. The root paste can be used to cure stomach aches, prevent abortion, and recover from tumors ³⁰. The roots of A. precatorius powder mixed with pure butter can be utilized to cure coughs ²⁶. The roots of A. precatorius can be utilized as medicine from snake bites by chewing ⁴⁰. A. precatorius roots extract in hot water can be given orally to use as an anticonvulsant and anti-malarial ⁴¹. In addition, the liquid broth from the dried root of A. precatorius taken orally is efficacious for the treatment of bronchitis and hepatitis ⁴². A paste of A. precatorius leaves and seeds can be rubbed on the head for gray hair ¹¹. Dry seeds of A. precatorius that are ground into a powder can be given orally to cure worm infestations in the digestive tract ²⁶. 

The bright red color of A. precatorius seeds attracts children's attention, so there are cases when children in rural areas who do not have knowledge of the A. precatorius plant eat its seeds which are poisonous when consumed ⁴³. Boiled A. precatorius seeds are often eaten by residents in several parts of India ^44,45. A. precatorius seeds also have several active compounds that are a source of insecticides and antimicrobials ⁴⁶. A. precatorius is considered a diuretic, expectorant, antidote, laxative, febrifuge, anodyne, aphrodisiac, hemostat, refrigerant, vermifuge, antimicrobial, emollient, vomiting reliever, sedative, laxative, and abortifacient ^47,48. In addition, A. precatorius is also used to cure blennorrhea, cancer, colic, seizures, diarrhea, diabetes, night blindness, snake bites, conjunctivitis, fever, rheumatism, jaundice, gonorrhea, headaches, ulcers, gastritis, ophthalmia, malaria, and chronic nephritis ⁴⁹. Soaked in hot water, A. precatorius seed extract can be taken orally to treat malaria ²⁶. Dry A. precatorius seed powder is used by various African ethnic groups as a natural contraceptive ¹¹. In addition, A. precatorius seeds can also be used to treat tuberculosis and painful swelling ⁵⁰.

Some of therapeutic uses 

A. precatorius has many therapeutic activitiy as listed in below:

Antimicrobial activity

The antimicrobial activity of the leaf, stem, and seed oil extracts of A. precatorius is quite effective in inhibiting the growth of several bacteria such as Klebsiella pneumonia, Bacillus subtilis, Corynebacterium spp, Enterococcus faecalis, Staphylococcus aureus, Streptococcus windosus, Staphylococcus epidermidis, and Escherichia coli through agar well diffusion techniques. A. precatorius roots extract also showed antimicrobial activity on various types of bacteria tested. Different solvent concentrations or fractions showed inhibitory activity against thirteen gram-positive and gram-negative bacteria. Through bioautography tests, it has been established that the antimicrobial activity of the A. precatorius extract is localized to specific chromatophores in the chloroform fraction ⁵¹.

Antihelmintic activity

The aqueous extracts of the roots and stems of A. precatorius were observed for their antihelmintic activities against schistosomes and cestodes. The aqueous extract of A. precatorius root indicated lethal antihelmintic activity combating cestodes at a concentration of 103 mg/ml. Meanwhile, aqueous extract of A. precatorius root at a concentration of 0.6 mg/ml and aqueous extract of A. precatorius stem at a dose of 1.5 mg/ml showed lethal antihelmintic activity against schistosomes. Tannins, steroids, terpenes, flavonoids, and alkaloids from A. precatorius may play a role in this antihelmintic activity ⁵².

Antimalarial activity

Isoflavaquinone-abruquinone compound isolated from A. precatorius extract showed antimalarial activity. Assessment of antimalarial activity was then carried out based on cytotoxicity and antiplasmodial activity. Cytotoxicity activity was evaluated in melanoma cells (A375), whereas antiplasmodial activity was evaluated by micro-radioactive methods. The assay of the A. precatorius extract was carried out at three diverse times in triplicate in 96-plate culture with the culture mostly at the ring stage at 0.5-1% parasitemia. A. precatorius extract showed IC50 values below 20 g / ml ⁵³.

Antifungal activity 

Dry A. precatorius seed extract at a concentration of 1% effectively inhibited the growth of Cryptococcus neoformans ⁵⁴.

Nephroprotective activity

The evaluation of the nephroprotective activity of the aqueous extract of the stem of A. precatorius was carried out to specify the restoring effect of acetaminophen and cisplatin-induced nephrotoxicity. The restoring effect of A. precatorius on HEK 293 cells damaged by acetaminophen and cisplatin was evaluated by the mitochondrial activity assay of MTS. The test results indicated that the water extract of the A. precatorius stem had the best recovery effect and could be utilized for the prevention or medication of kidney distraction ^55,56 

Immunomodulatory activity

Abrus agglutinin is one of the compounds dissociated from the seed extract of A. precatorius. This compound is similar to ML-1 with regard to the specificity of carbohydrates [gal (β1 → 3) gal / Nac], observed both in native (NA) and heat denatured (HDA) conditions for NK cell activation, cytokine secretion, murine splenocyte proliferation, and thymocyte proliferation in vitro with the aim of assessing its potential as an immunomodulator. HDA and NA activated splenocytes and induced the production of cytokines such as IFN-γ, IL-2, TNF-α, and TNF-β, which could exhibit a type of Th1 immune response. Native agglutinin abrasive and HDA-induced conditioned media of adherent splenocytes can stimulate non-adherent splenocytes and vice versa. Heat denatured abrasive agglutinin and induced NK cell activation at a much lower concentration than NA concentration, but the rate of NK cell activation was higher for NA. Thymocyte proliferation by HDA and NA was also evaluated. This study showed that Abrus agglutinin could be a potential immunomodulator in the original form as well as in the hot form ^57,58.

Neuromuscular activity

The neuromuscular activity of the ethanol extract of A. precatorius leaves was evaluated using isolated frog abdominal rectus muscles and phrenic nerve-diaphragm muscle preparations of rats and chicks. Ethanol extract of A. precatorius leaves hampered acetylcholine-induced contraction in rectus abdominis toad and rat phrenic nerve diaphragm muscle preparations. The effect depended on the dose of the ethanol extract of A. precatorius leaves. In addition, the ethanolic extract of A. precatorius leaves caused paralysis when injected intravenously into chicks and had no effect on direct electrical stimulation of the diaphragms of mice. The inhibitory effect on the diaphragm preparation of rat phrenic nerves from ethanol extract of A. precatorius leaves is strengthened in the presence of increased magnesium ions, reduced calcium ions, or decreased potassium ions. Thus, the ethanolic extract of A. precatorius leaves shows similarity to D-tubocurarine chloride in terms of the neuromuscular block pattern. Neither the petroleum ether nor the aqueous extract of the leaves of A. precatorius showed any significant changes in the skeletal muscle used in this study. Therefore, the nerve toxic component of A. precatorius leaves is particularly in the ethanol extract of A. precatorius ⁵⁹.

Antidiabetic activity 

An ethnobotany survey in five districts of the Nigerian state of Lagos was carried out by filling out a well-known semi-structured questionnaire for diabetes treatment ^60,61. In the survey, about 100 people answered, most of the respondents came from the Yoruba tribe ⁶². About half of the respondents had 20-30 years of experience in medicating diabetes by utilizing herbal plants (96%) without conventional treatment for diabetes. Among them, most of the men (76%) had knowledge of traditional diabetes treatment. They also developed an effective and easily recognizable diagnostic tool for diabetes. In the survey, fifty multi-component herbal recipes were covered, consisting mostly of liquid preparations. The drug in liquid form was often given orally without showing any serious side effects (92%). The main antidiabetic plants ⁶³ include A. precatorius, Blighia sapida, and Alchornea cordifolia. The leaves of these plants must be well squeezed in water until they release the juice, then the decoction can be used as a treatment for diabetes by using it as an infusion ⁶⁴.

Anti-inflammatory activity 

Two triterpenoid compounds, namely saponin 1 and saponin 2, and their derivatives namely acetate 3 and acetate 4 isolated from the A. precatorius plant were evaluated for their anti-inflammatory activity utilizing the croton oil ear model. The ear tissue parts of mice treated with anti-inflammatory agents were compared with the test treatment group. The results showed reduced inflammation in the ears of the mice tested. Triterpenoid compounds from A. precatorius showed anti-inflammatory activity but acetate indicated greater inhibition at concentrations of 300 µg and 600 µg. The acetate derivative of triterpenoid compounds was more effective at a concentration of 600 µg among all test treatment groups ⁶⁵.

Antifertility activity

Evaluation of the antifertility activity of A. precatorius seed extract managed intraperitoneally to adult male albino mice BALB/c strain on the integrity of spermatozoa DNA and sperm production. Daily sperm production was measured by calculating testicular spermatids in the Horwell chamber while DNA decay to epididymal spermatozoa was specified by comet test within 20 days of the experimental procedure. The administration of ethanol seed extract of A. precatorius (20 and 60 mg/kg) intraperitoneally caused a very significant mitigation in daily sperm production. Reversal in sperm production was monitored in all medicated animals after 20 days of therapy interruption. Similarly, a very significant increase in DNA damage was monitored in all medicated mice and no significant reversibility in DNA damage was monitored during the therapy period. This study proved that precatorius seed extract acted as an anti-fertility or contraceptive agent with a risk of DNA decay to spermatozoa and could cause teratogenic effects ⁶⁶.

Antiserotonergic activity 

The antiserotonergic activity of the ethyl acetate extract of A. precatorius leaves was examined on frog fundus strips utilizing sumatriptan as the standard drug. The ethyl acetate extract of A. precatorius leaves was effective in treating migraine headaches. The leaves of A. precatorius on soxhlet extraction with ethyl acetate showed the appearance of protein, saponins, amino acids, carbohydrates, tannins, alkaloids, as well as antiserotonergic activity on the frog fundus strips, which were shown (Graded dose response) compared to sumatriptan as a standard drug ⁶⁷. In another research, the anti-migraine activity of A. precatorius was demonstrated using fundus muscle preparations of Wister albino mice and male frogs using a Sherrington rotating drum. The muscle contraction influence of crude ethyl acetate and petroleum ether A. precatorius extract was carried out on both muscle preparations ⁶⁸.

Antidiarrheal activity 

Dry seed chromatography fraction of A. precatorius (10 mg/kg) was administered intragastrically to castor oil induced rats. This chromatographic fraction showed significant antidiarrheal activity ⁶⁹.

Antitumor activity 

Ethanol extract of A. precatorius leaves given intraperitoneally to mice showed inactive results in Sarcoma 180 (ASC) AP074 ⁷⁰. Aqueous extract of A. precatorius seeds administered intraperitoneally to mice showed active results in Sarcoma (Yoshida solid and ASC) ⁷¹. Aqueous extract of A. precatorius seeds given subcutaneously to mice indicated inactive results in Sarcoma (Yoshida ASC) AP012 ⁷².

Antispasmodic activity 

The chromatographic fraction of A. precatorius seeds at a dose of 0.2 mg/ml given to epinephrine-induced mice actively affected ACh-, PGE-2-, oxytocin- and epinephrine-induced contractions ⁷³.

Memory enhancer activity

The therapeutic potential of A. precatorius has been studied in a model of Alzheimer's illness by identifying glycochemical microglial cell activation (MGC) in autoptic brain samples. A. precatorius agglutinin confess MGC in the white matter of the brain, which exhibits stem-like cells and appears very dense in the proximal region of oligodendroglial cells. Lectin compounds from the A. precatorius plant have been studied to identify histochemically the activation of microglia cells in autopic brain samples from Alzheimer's illness subjects ¹⁰.

Toxicological

Although A. precatorius has many therapeutic properties, it should be noted that inaccurate dosage or intake can lead to life-threatening toxicity ⁷⁴. A. precatorius seeds could cause toxic effects at doses of 90 to 120 mg ⁷⁵. In addition, A. precatorius seeds contains abrin, which in doses of 0.0001 to 0.0002 mg/kg could be a natural poison ⁷⁶. The poisoning effects of ingested A. precatorius seeds can influence the kidneys, gastrointestinal tract, spleen, lymphatic and liver system ⁷⁷. Exposure to A. precatorius seed extract causes conjunctivitis, eye damage, and blindness ⁷⁸. Another symptom of poisoning is acute gastroenteritis with vomiting, nausea and diarrhea leading to shock, seizures, and dehydration ⁷⁹.

Conclusion

A. precatorius is a potential herbal plant that is good for use as a natural medicine. The stems, seeds, and roots of the A. precatorius plant each has their own traditional uses. In addition, the use of A. precatorius with an incorrect dose will cause toxic effects.

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