Rivea hypocrateriformis (Desr.) Choisy: A Review of its Ethno- medicinal uses, Phytochemistry and Biological activities

Rivea hypocrateriformis (Desr.) Choisy is a robust woody climbing shrub of the genus Rivea which is found in India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar and Thailand. R. hypocrateriformis is a promising medicinal herb with enormous helpful and wellbeing advancing impacts. R. hypocrateriformis has been utilized as a customary medication for a long time to treat rheumatic pain, fever, urogenital problem, snake bite, cough, piles, malaria, and skin disease. Apart from the traditional uses its leaves and young shoots are cooked and eaten as a vegetable and for preparation of bread with millet flour. This review comprehensively summarizes the up-to-date information on the botanical characterization, distribution, traditional uses, phytochemistry, pharmacology and toxicity study of R. hypocrateriformis. Phytochemical investigation has been revealed that alkaloids, glycosides, coumarins, flavonoids, xanthones, stilbenes, and other organic compounds are contained in R. hypocrateriformis. Crude extracts and isolated compounds have exhibited numerous pharmacological activities such as anovulatory effect, antifertility activity, antiarthritic, antimicrobial, anticancer, antioxidant, hepatoprotective, antilithiatic, antimitotic. R. hypocrateriformis is a promising restorative spice with monstrous remedial and wellbeing advancing impacts. Along these lines, further investigations on the bioactive mixtures and systems of R. hypocrateriformis are justified. Extra clinical and toxicological examinations are expected to assess its wellbeing.


Introduction
The family Convolvulaceae is a fairly large and homogeneous group comprising about 50 genera and nearly 1,700 species [1][2][3]. Rivea hypocrateriformis (Desr.) Choisy is a robust woody climbing shrub belonging to the family Convolvulaceae and is found in subtropical forests of India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar and Thailand [4]. The different parts of the plant are utilized for the treatment of different sorts of sicknesses, for example, malaria, cancer, mental disorders and to relieve pain. Evan though the plant is known for a large number of biological activities such as anti-oxidant, anti-implantation, antimicrobial, pregnancy irruption, as anticancer and as an antiarthritic [5][6][7][8]. Indigenous populaces of Tharparkar of Pakistan utilize this plant for the treatment of malaria fever and pain. Indians utilize these plants as hallucinogenic medication while Pakistani utilize this plant as psychoactive medication plant like different types of a similar family, for example, Rive corymbosa Hall and Ipomea violacea L. found in Mexico [9].
Argyreia bona-nox Sweet, Argyreia uniflora Sweet, Convolvulus hypocrateriformis Desr., Lettsomia uniflora Roxb., Modesta coriacea Rafin., Rivea bona-nox Choisy, Rivea fragrans Nimmo are the synonyms of R. hypocrateriformis. Taxonomical classification of R. hypocrateriformis is Kingdom: Plantae; Phylum: Tracheophyta; Class: Magnoliopsida; Subclass: Asteridae; Order: Solanales; Family: Convolvulaceae; Genus: Rivea [10]. It is likewise known by a variety of names, such as "Midnapore Creeper" in English, "Thor-kibel" or "Phang" in Hindi, "Sanjvel" in Marathi "Budthi Kiray" or "Musuttai" in Tamil, and "Niruboddi" in Telugu [11,12]. Customarily, its bark, roots, and leaves are utilized for the treatment of different diseases and issues [13]. Other than its customary uses, leaves and youthful shoots -cooked and eaten as a vegetable. The leaves are bubbled along with toppings and arranged dishes, for example, bhaji [14,15] or jowari flour which is then made into bread [14].The plant has high nutrient A substance (almost 2.34 retinal reciprocals), holding 75 -98% of this in any event, when cooked [16,17]. The leaves are a decent useful food. They contain a scope of dynamic mixtures and have gentle cell reinforcement potential. The plant is acceptable wellspring of energy and micronutrients and can be utilized as nutritious verdant vegetable in everyday life and explicitly in conditions, for example, when experiencing conditions like hack, skin sickness, and asthma [18].
It is also used as an ingredient in ayurvedic formulation "Parnasapancaka" used for the treatment of asthma [19]. Till date there is no review available on the R. hypocrateriformis. Therefore, the present review aimed at providing a more comprehensive analysis on the ethnomedicinal uses, phytochemistry, and biological activities. Furthermore, this study would highlight areas for future research on potential bioactivities of R. hypocrateriformis.

Research Methodology
The research methodology adopted for the selection of articles for this review is stipulated as flow chart in Figure 1.

Habitat
Midnapore Creeper is a robust woody climbing shrub, found in dry subtropical forests of India, Nepal, Sri Lanka, Pakistan, Bangladesh, Myanmar and Thailand. In India it is found in Assam, Bihar, Maharashtra, Rajasthan, and Tamil Nadu [20] (Figure 2).

Ethnomedicinal Uses
R. hypocrateriformis, an ordinary ayurvedic plant, is utilized by various local populace bunches in different manners due to the different helpful employments of its bark, roots, organic products, leaves and blossoms (Table 1). Apart from these ethnomedicinal uses its leaves and young shoots are eaten as a vegetable and roots are given after parturition. Cooked leaves of this plant are utilized as vegetable curry by the tribals of India. Leaves of this plant are used as vegetable by some hill dwelling Kandha tribes of Odisha [42]. Ayurvedic physicians use R. hypocrateriformis to prevent fertility in women. Leaves and young shoots are eaten as a vegetable and roots are given after parturition. Cooked leaves of this plant are utilized as vegetable curry by the tribals of India. This plant had maximum vitamin A activity and has the capacity of maximum (75-98%) retention of β-carotene upon processing [43,44].

Physiochemical and Nutritional Analysis
Loganayaki et al. studied the extractive value of leaf, stem and flower parts of R. hypocrateriformis with three different solvents chloroform, methanol and acetone respectively. Flower part of this plant exhibited higher extractive value 13.3%, followed by flower methanol extract 12.5%, flower chloroform extract 11.5%, leaf methanol extract 8.6%, Stem methanol extract 7.43 %, leaf acetone extract 5.9%, leaf chloroform extract 2.9%, stem acetone extract 1.87%, stem chloroform extract 0.7% [45]. Nutritional analysis of R. hypocrateriformis reported that its leaves contains Carbohydrate (%) 57 Table 2. Higher total phenolic content was reported in the flower acetone extract and flower methanolic [45].

Other compounds
Other compounds have been also reported ( Figure 11). N-acetylmuramoyl-alanine (33) belongs to the class of organic compounds known as acylaminosugars. These are organic compounds containing a sugar linked to a chain through N-acyl group. Two tripeptides His-His-Lys (34) and Asp-Arg-Asp (35), one bipeptide Glu-His (36) and one amino cyclitol streptidine (37) and one volatile compound methyl jasmonate (38) were reported in the root of R. hypocrateriformis [51].

Biological activities
Extracts from R. hypocrateriformis possess a broad spectrum of pharmacological activities. Past research affirmed that presence of phenolic acids and flavonoids is liable for its cancer prevention agent potential [53][54][55]. Past research uncovered that phenolic compounds are profoundly dynamic cell reinforcements, and such cancer prevention agent rich botanicals offer promising potential in the administration of degenerative illnesses. Phenolic compounds are auxiliary metabolites blended in plants because of ecological anxieties like assaults from microbes and bugs, UV radiation, and wounds [56]. These phytochemicals can kill hydroxyl extremists [57], superoxide anion revolutionaries [58], lipid peroxyl revolutionaries [59] and even to chelate metals, other than to assume an indispensable part in the steadiness of food items, just as in the protection components of natural frameworks [60]. These atoms likewise forestall oxidative misfortunes and have cytoprotective, mitigating, and adaptogen properties. The numerous pharmacological activities have been also reported, by the extracts and isolated bioactive compounds from R. hypocrateriformis including antiarthritic, anticancer, anti-inflammatory, antimicrobial, anovulatory, antioxidant, hepatoprotective, antifertility, antimitotic, antiproliferative, antilithiatic activity. Simultaneously, several in vitro and in vivo studies on pharmacological profile of R. hypocrateriformis are under way. Scientific exploration has revealed that different types of R. hypocrateriformis extracts possess multiple bioactive attributes (Table  3).

Toxicity Study
The toxicity study of PPFRH indicated, there was no adverse effect on mortality detected in Swiss albino mice and Wistar albino rats that were administered up to 4000 mg/kg, orally. This was observed during 24 h period, and the extract was found to be safe at the given dose [17].

Conclusions
This survey sums up the wide pharmacological exercises of R. hypocrateriformis and its dynamic constituents dependent on customary writing and current proof. Some toxicological examinations on R. hypocrateriformis are additionally announced. Our investigation gives an exhaustive and inside and out assessment of R. hypocrateriformis and shows that it is a promising conventional medication that can be abused for its helpful and tonic advantages. Leaves of R. hypocrateriformis are a good source of energy and micronutrients. It possesses zinc, phosphorous, magnesium, and calcium along with protein, fat, and carbohydrate. It has the highest amount of energy content. The study revealed that the plant is good source of energy and micronutrient and can be used as nutritious leafy vegetable in daily life and specifically in conditions such as cough, skin disease, and asthma. Earlier study revealed that bergenin (10), a C-glycoside isolated from the R. hypocrateriformis exhibited hepatoprotective, antiarrhythmic, neuroprotective, antifungal, anti-inflammatory, immunomodulatory, anti-HIV, antifungal, antihepatotoxic, wound and ulcer healing potential. Calophyllolide (25) has been reported to exhibit some biological activity, including anti-inflammation, lower capillary vascular permeability, anti-cancer, anti-microbial, and anti-coagulant properties. Earlier researches also reported that stilbene trimers like α-Viniferin (23) exhibited AChE activity in a dose-dependent manner. Therefore, the further clinical studies are warranted these potential derivatives of R. hypocrateriformis for development of novel therapeutic approach. Earlier research reported that norbergenin (11), is the O-methyl derivative of bergenin (10) exhibited the neuroprotective potential on rat cortical neurons. Despite the fact that R. hypocrateriformis has been utilized broadly as a therapeutic spice and in a few tonics, quality norms have not yet been set up. The current logical techniques are not agreeable to control the nature of R. hypocrateriformis. The nature of R. hypocrateriformis is affected by the environment and picking time, and the classifications of dynamic segments contrast broadly among various territories and picking times; along these lines, quantitative distinguishing proof is fundamental for control the nature of restorative materials, which will likewise dispose of contaminated and assurance the remedial impact of R. hypocrateriformis. It is important that the current examinations on R. hypocrateriformis are lacking. The particular systems of activity and material premise of the adequacy are not extremely clear, and its clinical worth has not been totally investigated at this point. Along these lines, the deliberate examinations on R. hypocrateriformis ought to be attempted to represent its ethnomedicinal use.
Author Contributions: Conceptualization, investigation, data curation, writing-original draft preparation, writing-review and editing, M.M., A.K., C.H., S.D., D.T., M.C. and R.P. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Data Availability Statement: All the data are included in the present study.