1. Introduction

Humans have been dependent on plants since the ancient times for various reasons such as food, shelter, and medicine [1]. Medicinal plants are the primary source of health benefits in various communities of the world [2]. More than 80% of the world’s population is reported to use plant-based medicines as primary healthcare as they are easily available and safe to use [3]. Recently, researchers have developed traditional knowledge about medicinal plants which can fulfill the current gap in therapeutics, nutraceuticals, drug discovery, and development [4]. Especially in developing countries, the reliance on plant medicine is a typical basis for addressing the ethnomedicinal knowledge in therapeutics from different ethnic communities [5].

Altogether 68 names of species are recorded under the genus Catunaregam belonging to family Rubiaceae [6]. The particular species Catunaregam spinosa (Thunb.) Tirveng. (Figure 1) is a shrub with thorns which is distributed up to 4000 ft. from the sea level [7]. The other synonyms of this species are given in Table 1 [6]. C. spinosa, known as Madana in Sanskrit, Madanphal in Nepali, and emetic nut or mountain pomegranate in English, is a deciduous shrub with approx. 5 m of height, leaves are ovate, simple, shiny, and pubescent [8], and flowers are white solitary and possess a honey-like fragrance [9]. This plant has been reported from various parts of India [10], Nepal, Bangladesh, South China [11], and the African subcontinent [12]. C. spinosa is reported to be distributed in tidelands of semitropical and subtropical areas [13]. The ancient medicinal systems of Ayurveda and Siddha use this plant to treat various types of symptoms and it is still in use [14]. “Rasayana,” a kind of clinical specialties in Ayurveda, uses this plant for promoting good habits in the dietary regimen [15]. People in India and Brazil use this plant for treating food poisoning, inducing vomiting, and treating allergy and inflammation [16]. The presence of various important phytoconstituents such as phenols, flavonoids [17], triterpene saponins [18, 19], hemolytic saponins, randianin [20], iridoids [21], dihydroisocoumarin [13], and many more other phytoconstituents is reported from various parts. Several studies have reported the modern pharmaceutical activities of C. spinosa such as piscicidal [22], molluscicidal [23], antioxidant [8], anti-inflammatory, antidiabetic, and antihyperlipidemic [24] activities. The isolated compounds are not well studied for the possibility of drug discovery pathways. It is important to have a clear idea of this medicinally important plant and its scientific progress. The review of the current state of C. spinosa and its overall perspective related to ethnomedicinal importance and modern medicine is still lacking. Thus, this review aims to collect and analyze the current status of traditional uses, phytochemicals, and pharmacological activities from the available scientific information.

2. Methodology

The scientific information of C. spinosa was collected from various online databases such as SciFinder, Scopus, Google Scholar, PubMed, Web of Science, and ScienceDirect. Additionally, the books, proceedings, comments, and editorials were used as secondary sources. The scientific names and their synonyms were cross-checked from the database available in the website of “The Plant List” (http://www.theplantlist.org/). The articles of better quality with sufficient taxonomical, ethnomedicinal, and pharmacological information were selected while preparing this review.

3. Traditional Uses in Medicine and Food

The fruit of C. spinosa is traditionally used to treat various symptoms (Table 2). Almost all parts of the plant have been used as a traditional medicine in Ayurveda and fruits have been reported to be used in medicine as well as in food. This plant is reported to treat ulcers, inflammation, tumors, wounds, and skin diseases [7]. People from the upper hilly region of India used its bark for curing diarrhea and dysentery [25]. The fruits or pulps of this plant are used as an abortifacient [26] and nauseant [11], as well as for treating asthma [27, 28]. The fruit of C. spinosa is also taken as a nutrient or diet.

4. Chemical Constituents

Various flavonoids, alkaloids, tannins, lignans, terpenoids, and volatile oils have been reported from this plant. The triterpene, saponins [21], and iridoid glucosides were isolated [42] from the fruits of C. spinosa. Three triterpenoid saponins, 3-O-[β-D-glucopyranosyl-(1⟶3)-β-D-6-O-methyl-glucuronopyranosyl oxy]-2β-hydroxy-olean-12-en-28-oic acid, 3-O-[β-D-glucopyranosyl-(1⟶2)-β-D-glucopyranosyl]-olean-12-en-28-oic acid, and 3-O-[β-L-rhamnopyranosyl-(1⟶3)-β-D-glucuronopyranosyl-(1⟶2)-β-D-glucopyranosyl-(1⟶2)-β-D-glucopyranosyl]-12-en-28-oic acid, and two triterpenoids, oleanolic acid and 3β,23-dihydroxy-olean-12-ene-28-oic acid, were isolated from fruits [43]. From the stem bark of C. spinosa, the compounds named catunaregin and epicatunaregin were isolated [44]. Many triterpenoid saponins such as catunarosides were reported [45] from the n-BuOH extract of the stem bark of this plant. There have also been studies on nutritional contents of the fresh fruit of this plant and they were reported to contain a high amount of carbohydrate [38]. 11-Methylixoside was isolated from the bark of C. spinosa [46]. The bioactive compounds are enlisted in Table 3 and their structures are in Figures 2–6.

5. Pharmacological Activities

Due to the widespread traditional uses, C. spinosa extracts and compounds have been subjected to various pharmacological activity evaluations. This plant has been studied widely for its pharmacological activities, mainly antibacterial, antioxidant, anti-inflammatory, antimicrobial, anticancer, and antifertility activities. Few studies have reported sedative and analgesic activities. Most of the activities are based on random screening rather than traditional knowledge, which cannot provide the correlation between ethnomedicine and modern pharmacological activities. Some studies carried out on C. spinosa are discussed in the following section.

6. Toxicological Aspects

Acute toxicity study showed that the aqueous and alcoholic extracts of C. spinosa at a dose of 2000 mg/kg in a Swiss albino mice model were found to be nonlethal [14]. Another study regarding the toxicity of 11-methylioxoside obtained from the bark of C. spinosa was reported by Jangwan et al. [46]. Upon administrating the single dose of 5000 mg/kg extract of C. spinosa in Wistar albino rats, no mortality was observed. However, when administrating the different doses of 200 mg/kg, 2000 mg/kg, and 5000 mg/kg continuously up to 14 days, the mortality observed was 0%, 25%, and 50%, respectively. The result was supported by a change in biochemical parameters and histopathology reports [60].

Brine shrimp lethality assay was done to study the cytotoxic activities of C. spinosa leaf extract and lethal concentration (LC₅₀) was determined. The LC₅₀ values of water and ethanol extract were 0.94 and 0.23 µg/ml, respectively [12]. A similar study was done in the methanolic extract of the stem and the LC₅₀ value was found to be 1.32 µg/mL [29].

7. Conclusion and Future Prospects

C. spinosa is reported to be used in traditional medicine as well as in dietary regimens. Almost all parts of the plant have been used in traditional medicines such as leaves, fruits, stem, stem bark, fruit bark, and root bark. Fruits are also used in food. Various classes of compounds such as polyphenols, flavonoids, terpenoids, triterpenoids, and saponins are reported to be the main constituents found in this plant. The diverse pharmacological activities such as anti-inflammatory, antimicrobial, antidiabetic, antioxidant, and hepatoprotective activities have been investigated with promising results. Despite those promising results, many studies are based only on the in vitro models, and mechanisms of action are not well studied. Some of the research lacked the proper use of positive and negative control in the experiment setting. The in vivo studies were performed with very high doses of extracts and seem practically less efficient. Some ethnopharmacological reports show that this plant has been used to treat ulcer symptoms and acidity; however, pharmacological activities were not performed to evaluate these activities. Future research work must correlate the traditional knowledge with the isolation of active constituents and corresponding pharmacological significance. Along with this, the details of toxicological activities if studied can pave the way to develop new therapeutic agents.

Conflicts of Interest

The authors declare no potential conflicts of interest.

Authors’ Contributions

DT conceived the idea and prepared the first draft of the manuscript. DB and KRS contributed to the literature survey. HPD contributed to the preparation of the first draft and revised the manuscript. All authors read and approved the final version of the manuscript before submission.