RJPS Vol No: 14 Issue No: 1 eISSN: pISSN:2249-2208
Nisha Pyngrope* , V B Narayana Swamy, Akila E, Pruthvi N
Department of Pharmacognosy, RR College of Pharmacy, Bangalore, Karnataka.
*Corresponding author:
Nisha Pyngrope, Department of Pharmacognosy, RR College of Pharmacy, Chikkabanavara, Bangalore, Karnataka – 560090. E-mail: nanapyngrope359@gmail.com
Received date: February 18, 2022; Accepted date: April 20, 2022; Published date: June 30, 2022
Abstract
The genus Codiaeum, often known as the miracle shrub is utilized by indigenous people to treat diarrhoea, stomach ache, external wounds, intestinal worms, and ulcers. The goal of the current review is to examine the literature for updated pharmacological characteristics of Codiaeum species (Euphorbiaceae). This review may be useful to researchers in focusing on the priority areas of study that are yet to be discovered. This information has been gathered from numerous books and journals. This review gives the details of pharmacological activity, continuing and developing fields of research of this plant, particularly in the field of pharmaceuticals.
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Introduction
Importance of Herbal Medicine
The word “medicinal plant” describes various types of plants used for medicinal activity. The word “herb” comes from the Latin word “herba” and an old French word “herbe.” Herbs are group of plants, except vegetables and other types of plants which are used for macronutrients or aromatics or fragrances that are used for flavoring or decoration of food and for medicinal property. Any part of the plant might be regarded as a “herb”, which includes leaves, roots, flowers, seeds, root, bark resin and pericarp. Herbs have been used for culinary, healing, and fragrant purposes and they are used for spiritual purpose in some cases.
Ultramodern pharmaceuticals had their origins in crude herbal drugs. Presently some medicines are still uprooted as fractionate or separate composites from raw herbs and are also purified to meet pharmaceutical norms.1
Hundreds of years ago, traditional physicians provided the treatment using herbal drugs based on the curative experiences. Herbal drugs have gained accumulative popularity even in the present medical practices. The extensive use of herbal products since ancient times is mainly due to their easy accessibility, affordability, effectiveness and safety.2
Herbal medicine, sometimes referred to as botanical medicine or herbalism, involves the utilization of herbs or parts of herbs, to treat injuries or illnesses.3 Herbal medicine is the branch of science which involves medicinal plants for prevention as well to treat diseases and afflictions, promoting health and healing.4 Herbal medicine is a medicine or preparation derived from herbs or herbal parts which is considered for specified uses. Herbal medicines are the oldest forms of health care known to mankind.5
World Health Organization (WHO) has described medicinal drugs as consummated, marked therapeutic products that contain active constituents, entire, upper or lower parts of the plant or different plant substance or mixtures. WHO also set special guidelines for the evaluation of the safety, effectiveness, and standardization of herbal drugs and their products. WHO also estimated that around 80% of total world population currently is using medicinal plant drugs for primary healthcare. Herbal drug is a major element in traditional drugs and a common element in Ayurveda, homeopathic, naturopathic and other alternative medical systems.6
Codiaeum Species Details
Plant Description
Codiaeum species generally known as Croton and Joseph’s Coat, belongs to the family Euphorbiaceae. It is the famous ornamental plant because of visual leafage colors and differed leaf figures. These are native to Philippines, India, Indonesia, Malaysia, Thailand and Sri Lanka. More than 200 kinds of crotons exist on the globe, attainable in different leaf sizes, shapes and color patterns. Croton is an evergreen shrub of up to 6 m height but generally is maintained at 60-90 cm and grows easily in areas with humid climate. Young leaves are generally green, bronze, yellow, or red, and later changes to gold, cream, white, scarlet, pink, maroon, purple, black or brown. Occasionally the same plant shows variations in the forms of leaves and color and the flowers are small, long, axillary, usually unisexual racemes. Fruits are globular capsules, measuring 3-8 mm in diameter.7
Traditional Uses
Codiaeum genus leaves are traditionally used to treat cancer, constipation, diabetes, digestive problems and dysentery, external wounds, fever, hypercholesterolemia, hypertension, inflammation, intestinal worms, malaria, pain, ulcers and weight loss. The leaves of the Codiaeum variegatum are being used as a tonic, the flowers are used to cure flat worms, the fruits of the plant are used to treat dysmenorrhoea, the seeds are used as a purgative, the bark is used to treat dyspepsia, and the roots of the plant helps to treat dysentery. The bark as well is utilized to treat chronic liver enlargement and recurrent fever.8
Phytopharmacological Properties
The laminas of coriaceous conserve cytotoxic metabolites that may be applied as alternative substances with pharmacological purposes against infections caused by microorganisms, mainly viruses. In case of Codiaeum species, its coriaceous laminas and the latex of stems have bioactive action of medicinal importance, among which the important are as follows:
A. Healing action: The secondary metabolites available in the coriaceous laminae of Codiaeum variegatum, from the naturist point of view are being utilized in the popular medicine for treating various diseases.9
B. Antiviral activity: Vegetative latex extracts of Codiaeum variegatum show a high antiviral potential against influenza virus.9
C. Renal condition: The positive effect of vegetative latex of Codiaeum variegatum on kidney problems associated with urinary retention has been reported.9 The chromatographic fractions of Codiaeum variegatum had relevant anti-FLUAV activity which is a bio-guided screening against influenza A virus (FLUAV).10
Phytoconstituents of Codiaeum species
Caryophyllene oxide (58.2 percent) and (Z)—farnesene were the primary elements of C. variegatum (L.) Blume f. lobatum cv. Disraeli (19.6 percent). Linalool (39.3 percent), 1,2,4-trimethylbenzene (21.0 percent), -pinene (21.6 percent), and -pinene (17.9 percent) were all detected in substantial levels in C. variegatum var. pictum ‘Congo.’ The principal constituents of C. variegatum (L.) Blume f. taeniosum cv. were phytol (17.8 percent), -bisabolene (9.6 percent), and linalool (8.9 percent). C. variegatum (L.) ‘Dreadlocks,’ was dominated by -ionone epoxide (29.7 percent), -muurolene (20.5 percent), naphthalene (16.3 percent), and (E)-ionone (14.8 percent).11 The GC-MS chromatogram of a chloroformic extract of Croton bonplandianus aerial parts revealed 59 peaks, suggesting 59 phytochemicals. 1,1,2,2-Tetra chloro ethanes, 2,1,1,3-Trichloro acetone, Chlorobutyryl chloride, and Penta chloroethane are among them. Also Avlothane, 1,2-chlorobutyryl chloride L-Camphor, 4-Propyl Benzaldehyde, 3.2,3-Dichloro2-Methylpropanol Curcumene, Beta Farnesene (E), l-zingiberene, Cedr-8- ene, Cedr-8-ene, Cedr-8- ene, 3,5-Dimethylbenzylbromide Curcumin (Beta Curcumene), Cadina.12 Carbohydrates (glycosides), flavonoids, sterols (triterpenes), alkaloids, and proteins are among the phytoconstituents found in C. tiglium seeds. In the dried aqueous seeds extract, the protein was hydrolyzed into free amino acids, necessary amino acids (20.71 percent), and nonessential amino acids (79.29 percent). Furthermore, mucilage in dried aqueous seeds extract and total detected sugars account for 81.21 percent of total mucilage hydrolyzate. The total saturated fatty acids (13.68 percent), total monoenoic fatty acids (34.49 percent), total dienoic fatty acids (45.76 percent), and total recognized fatty acids in the saponifiable materials of the petroleum ether extract (93.93 percent). Saturated hydrocarbons (40.73 percent), unsaturated hydrocarbons (18.93 percent), fatty alcohols (10.08 percent), sterols (10.61 percent), and total recognized chemicals made up the unsaponifiable matter (80.35 percent). There were also four substances (sitosterol, -amyrin, and oleanolic acid).13
Active Constituent of Codiaeum species
The major bioactive constituents of Codiaeum species includes alkaloids, carbohydrates, glycosides, steroids, flavonoids, coumarins, saponins, fatty acids, tannins, protein and amino acids, gum and mucilage, terpenoids, anthroquinones and phenols in different parts like root, stem and leaf extracted using different solvents.14
A review reported a total of 399 new compounds, including 339 diterpenoids as chemical constituents of Croton species. Croton species are reported with diterpenoids as characteristic components.15 Several species of Croton have a red sap, with some species containing proanthocyanidins and/or alkaloids.16 Presence of volatile oil components is indicated by the aromatic nature of some species in the genus.17,18
Antioxidant Potential of Codiaem species
The anti-oxidant potential of various Codiaeum species is tabulated in Table 1.
According to Baviskar et al., the leaves of Croton caudatum might be a good source of natural antioxidants. The antioxidant activity of various quantities of ethanol extracts of Croton caudatum leaves were evaluated using four test techniques, that is the DPPH radical scavenging assay, the reducing power ability assay, the hydrogen peroxide scavenging assay, and the thiocyanate method. In all the experimental methodologies, ethanol extract of Croton caudatum leaves have shown effective antioxidant activity.19
The phytochemical analysis of C. floribundus and C. urucurana reports the availability of triterpenes and/ or steroids, flavonoids, and tannins in both species, but only C. floribundus contained purines. The antioxidant action of C. floribundus extract was the highest.20 In the assay of DPPH free radical scavenging experiment, the antioxidant fraction of C. urucurana Baillon’s crude essential oil had an IC50 of 1.05 mg mL-1. 21 The antioxidant components found in C. zambesicus leaf extract supports the plant’s ethnomedicinal application in oxidative-stress-related disorders in folk medicine.22
C. celtidifolius crude extract, fractions, subfractions, and isolated compounds have all shown antioxidant activity in vitro, can scavenge superoxide anions at a given concentration of 100g mL–1. 23 Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of scavenging property and it was observed in WRL-68 cell line.24 A study based on the antioxidant evaluation of ethanolic extract of Croton hypoleucus in a frame of a thioacetamide-induced (TAA) liver damage model in rats was investigated by Thania Alejandra et al. 25 Evaluation of antioxidant efficiency of C. tiglium seeds extracts after incorporating silver nanoparticles was conducted by Ahmed Youssef et al. This study aimed to enhance the efficiency of different Croton tiglium seeds extracts by incorporation of silver nanoparticles (Ag-NPs) through raised up cytotoxicity against growth of human colon cancer cells. C. tiglium seeds contained various phytoconstituents. e.g., carbohydrates (glycosides), flavonoids, sterols (triterpenes), alkaloids, proteins. Additionally, incorporation of Ag-NPs into the extract caused no toxicity in the experimental animals when administrated orally.13
In vivo pharmacological activities of Codiaeum species
In vivo pharmacological activities of Codiaeum species is tabulated in table 2.
Croton hypoleucus aerial parts ethanolic extract demonstrated hepatoprotective action and is used to treat liver disorders.26 Solvent fraction and crude extract of Croton macrostachyus is reported to possess hepatoprotective properties. The hepatoprotective actions of plant extracts might be attributed to their scavenging and antioxidant properties, which are caused by the presence of various phytochemicals like polyphenols, flavonoids, saponins, and alkaloids.27 C. macrostachyus aqueous extract obtained from leaves reveals that it possesses hepatoprotective activity and may be considered as a source of new hepatoprotective drugs.28
Administration of crude extract obtained from C. macrostachyus root on pyloric ligation-induced ulcer in rats resulted in a considerable decrease in gastric acidity and stomach discharge, with a significant rise in pH and mucus content.29
C. macrostachyus stem bark extracts (ethyl acetate, methanol, and isobutanol) exhibit antiplasmodial action (both chemotherapeutic and chemoprotective) against Plasmodium berghei. 30 Degu A et al., reported that the chloroform and methanol fractions of C. macrostachyus leaves possess significant anti-diarrheal activity.31 Croton zambesicus crude leaf extract (200 – 600 mg/kg) substantially prevented ulcers caused by the ulcerogens employed (indomethacin, ethanol, and histamine). The findings of this study imply that Croton zambesicus leaf extract has antiulcer efficacy, lending support to the plant’s ethnomedical usage.32
C. zambesicus extract has shown strong analgesic and antipyretic action, but only a modest anti-inflammatory activity. These activities are carried out via the extract’s core activity in the brain. These findings support its longheld usage for treating of malaria symptoms.33 Under the current experimental circumstances, a study found that Croton malambo bark aqueous extract possesses anti-nociceptive and anti-inflammatory properties. The TD50 was calculated to be 12.3 mg/kg (95% confidence interval: 10.3–14.6 mg/kg). The Croton malambo bark aqueous extract is safe at all the given doses in the above study even with high dose level of 4096 mg/kg. There was no toxic effect found with the higher dose also. So LD50 value forthe same plant could not be determined.34
The Croton bonplandianum Baill leaves extract of petroleum ether and ethanol used to treat earthworms revealed to be more effective than the usual medicine Albendazole at the same concentration.
The report proved that the extracts in petroleum ether and ethanol were more efficient than the standard drug, while the aqueous extract was observed somewhat less effective than the standard drug. As a result, the research supports the cultural usage of Croton bonplandianum Baill as an antihelmintic medication.35
According to a study on C. lobatus leaves extract, the median fatal dose was determined to be more than 5000 mg/kg, but apparent side effects and death were not documented at this dose. Following this, anti-diabetic activity was also determined. The body weight of diabetic untreated rats declined considerably after comparing with control and treated groups of rats; however, no significant variations in relative organ weight of rats were observed at the dose of 100, 200 mg/kg, orally.36 Croton zambesicus ethanolic leaf extract was studied and showed antimalarial efficacy, after studying the capacity to reduce Plasmodium berghei infection in mice in all three assessment tests.37
At day 3 post-wounding, it was discovered that treatment with 20% Croton zehntneri decreased oedema and exudates to a similar extent as dexamethasone. Croton zehntneri or trans-AT therapies had no effect on inflammatory cell infiltration or angiogenesis. With 20 percent Croton zehntneri ethanolic leaf extract in trans-AT-treated animals, however, wound closure was accelerated, with an increased number of fibroblasts and collagen fibres. Croton zehntneri ethanolic leaf extract has strong wound healing activity, indicating that it has medicinal potential.38 Anthelmintic activity of Croton zehntneri essential oils was investigated by Vasconcelos et al. 39 In streptozotocin (STZ)-induced diabetic rats, an aqueous extract of the stem barks of Croton cuneatus Klotz (Euphorbiaceae) was tested for hypoglycemic action. The activity of C. Cuneatus aqueous extract was compared with the reference standard medication glibenclamide. Results of the study revealed the antidiabetic activity of this herb in streptozotocin induced diabetes rat models.40
Croton cuneatus Klotz. (Euphorbiaceae) aqueous extract was investigated for antinociceptive effects in mice utilising chemical and thermal test methods. The aqueous extract of Croton cuneatus at a dose of 7 mg/ kg has shown a strong anti-inflammatory effect when compared to regularly used nonsteroidal medications such as ketoprofen, sodium diclofenac, and aspirin (acetylsalicylic acid).41 The viability of L. amazonensis was examined using C. Cajucara essential oil and pure linalool. Promastigotes had LD50 of 8.3 ng/mL for essential oil and 4.3 ng/mL for pure linalool, whereas amastigotes had LD50 of 22.0 ng/mL for essential oil and 15.5 ng/mL for purified linalool.42
In vitro Pharmacological Activities of Codiaeum Species
The in vitro pharmacological activities of Codiaeum species is tabulated in table 3.
The essential oil from the entire part of the specimen of C. heliotropiifolius showed antibacterial activity against B. subtilis. 43 Ethanolic extract of the stem bark of Croton heliotropiifolius Kunth (Euphorbiaceae) inhibited acetylcholinesterase significantly in vitro using a dilution spectrophotometric assay and exhibited antifungal activity against Candida albicans as found by thin layer chromatography (TLC) bioautographic assay.44 The in vitro antifungal efficacy of ethanolic extract of Croton aromaticus leaves against mycelial growth and spore germination of postharvest fungal infections was investigated and the C. aromaticus L. leaf extract qualitative phytochemical examination suggested the presence of alkaloids, terpenoids, quinones, phytosterols, and flavonoids.45
The three essential oils derived from Croton are the richest in hydrocarbons, monoterpenes, hydrocarbons, and oxygenated sesquiterpenes and it was found that C. adipatus was selective for B. subtilis and C. albicans, C. thurifer for S. aureus, and C. collinus had antibacterial action against B. subtilis and C. albicans. 46 Muriel Sylvestre et al., studied and reported about the essential oil analysis and anticancer activities of Croton flavens L. leaf essential oil.47 Amoebicidal activity of the aerial portions of C. pallidulus, C. ericoides, and C. isabelli was studied and it was reported that essential oil of C. ericoides was the most active, killing 87 percent of trophozoites at 0.5 mg/mL concentration.48
The Salmonella/microsome test was used to evaluate the mutagenic activity of Croton lechleri sap (Salmonella typhimurium) and yeast cells of Saccharomyces cerevisiae. According to the findings, Croton lechleri sap contained oxidative damages generated by apomorphine in Saccharomyces cerevisiae. 49 Maria Ines Lopez et al., examined leaf n-hexane, dichloromethane, and extracts from methanol of C. macrobothrys for the in vitro antiproliferative efficacy on cell lines.50 The potential antimicrobial activity of plant extracts and substances isolated from Croton antisyphiliticus and C. urucurana species was evaluated against strains of Staphylococcus aureus isolated from mastitis-infected cow milk, and it was concluded that C. urucurana had the most promising antimicrobial activity against strains of S. aureus causing bovine mastitis.51
Croton sonderianus antibacterial diterpenes have shown biological activity in preliminary qualitative antimicrobial testing employing gram negative bacteria such as Pseudomonas aeruginosa and Escherichia coli. 52 Essential oils isolated from fresh leaves have a chemical composition and antimicrobial action and branches (EOB) of Croton campestris were examined.53 Lidiane Gomes de Arujou et al., investigated the antibacterial properties of Croton argyrophyllus essential oil and found to be potentially active against Staphylococcus aureus. 54
Dermatophytosis is a common dermatological issue caused mostly by the genera Trichophyton, Epidermophyton, and Microsporum. The antidermatophytic activity of Croton tiglium stems, leaves, and seeds was investigated in this study. Furthermore, the ethanolic extract of C. tiglium has shown potent antifungal activity against dermatophytes such as T. mentagrophytes, T. rubrum, and E. floccosum. 55 The C. damayeshu isolated leaves were assayed for their larvicidal, antifungal, and α-glucosidase inhibitory activities, and it was found to possess larvicidal activities against Plutellaxylostella with LC50 values of 0.19, 0.16, and 0.26 μM, respectively, comparable to the LC50 of 0.14 μM for the positive control, flubendiamide.56
Vinayaka et al., noticed and examined the antibacterial and antifungal activities of C. gibsonianus Nimm. Grah methanolic extract. The extract was found to cause a greater inhibition of P. aeruginosa, followed by E.coli and S. aureus. 57 Gomes et al., reported the phytochemical composition as well as antibacterial capabilities of the essential oil of C. limae leaves, and C. limae was considered as the plant with welldocumented antimicrobial activity.58 By using the agar well cut diffusion method, the antifungal activity of several plant components such as hexane, chloroform, ethyl acetate, and methanol extract were examined against three fungal species, for example, Aspergillus niger, Candida albicans, and Candida tropicalis. The outcomes were compared to Ketoconazole, which was utilized as a control. At different concentrations, all the extracts demonstrated varying antifungal properties, and the inhibitory efficacy varied from solvent to solvent.59
C. tricolour extract showed substantial inhibitory efficacy against numerous Candida species, according to microbiological studies. As a result, C. tricolour stem extract is a potential natural medication for treating candidiasis.60 From the natural acetophenone isolated from Croton anisodontus, eight chalcones were synthesized. Chalcones (E)-3-(furan2-yl)-1-(2-hydroxy3,4,6-trimethoxyphenyl propionate) in vitro antifungal activity was demonstrated. -2-en-1-one (8) (E)-1-(2- hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl) prop2-en-1-one (6) were identified as chalcones with superior fungal suppression against C. albicans. 61
Casbane Diterpene from C. nepetaefolius was evaluated for antibacterial activity against oral pathogens in planktonic forms and biofilms, showing MIC values of 62.5 g/mL against Streptococcus oralis and values ranged from 125 to 500 g/mL against S. mutans, S. salivarius, S. sobrinus, S. mitis, and S. sanguinis. At 250 g/mL, Casbane Diterpene inhibited the production of S. mutans biofilms.62 The property of antimicrobial activity of the methanolic root extract and compounds isolated from Croton membranaceus against bacteria was investigated, and the results revealed that the gomojoside H is a potent antibacterial compound, and its presence appears to explain in part the antimicrobial activity of the C. membranaceus root extract.63
The antibacterial screening of C. hieronymi Griseb oil was evaluated, and the root oil was shown to be active against E. coli, K. pneumoniae, and C. albicans at 102 g/mL, while the leaf oil exhibited high action against E. coli and K. pneumonia. 64 C. pullei methanol and hexane extracts were subjected to study for antibacterial activity against Gram-negative bacteria, Gram-positive bacteria, and yeast species responsible for various forms of acquired infections in people and, more often, antimicrobial resistance. Both extracts inhibited the examined microorganisms, with the methanol extract having a greater impact than the hexane extract.65 The chemical variety from Croton tetradenius essential oil was conducted to evaluate their antibacterial activity. The results also demonstrated the chemical variety of C. tetradenius essential oil and its ability to limit the growth of food-borne spoilage bacterial strains.66
Conclusion
According to the preceding review, the plant species have traditionally been utilised for various medicinal purposes. The Codiaeum plant species have been scientifically proven to be powerful analgesic, anti-inflammatory, cardioprotective, anthelmintic, antibacterial, antifungal, and cytotoxic agents. The phytoconstituents found in plant species are accountable for the activities. More studies are needed to identify the elements that are responsible for the biological activities. It was also found that no clinical studies have been investigated so far. As a consequence of the current study of literature and Ayurvedic texts, it was found that the plant species have great therapeutic potential. The traditional and ethnomedical literature revealed that the plant species are extremely useful and safe for medicinal usage. This review also enlightens about the natural drug development through reverse pharmacological methods.
Conflicts of Interest
Nil
Supporting Files
References
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