Ranbir Chander Sobti
Naveen Kumar Arora · Richa Kothari
Editors
Environmental Biotechnology:
ISBN 978-981-10-7283-3 ISBN 978-981-10-7284-0 (eBook)
https://doi.org/10.1007/978-981-10-7284-0
Library of Congress Control Number: 2018957141
© Springer Nature Singapore Pte Ltd. 2019
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Contents
Part I Biodegradation and Bioremediation
1 Biochar for Effective Cleaning of Contaminated
Dumpsite Soil: A Sustainable and Cost-Effective
Remediation Technique for Developing Nations................................... 3
Paromita Chakraborty, Moitraiyee Mukhopadhyay, R. Shruthi,
Debayan Mazumdar, Daniel Snow, and Jim Jian Wang
2 Scope of Nanoparticles in Environmental Toxicant Remediation....... 31
Anupam Dhasmana, Swati Uniyal, Vivek Kumar, Sanjay Gupta,
Kavindra Kumar Kesari, Shafiul Haque, Mohtashim Lohani,
and Jaya Pandey
3 Removal of Inorganic and Organic Contaminants from
Terrestrial and Aquatic Ecosystems Through
Phytoremediation and Biosorption......................................................... 45
Dhananjay Kumar, Sangeeta Anand, Poonam, Jaya Tiwari,
G. C. Kisku, and Narendra Kumar
4 Environmental Health Hazards of Post-Methanated
Distillery
Effluent and Its Biodegradation and Decolorization............................ 73
Sangeeta Yadav and Ram Chandra
5 Heavy Metal Contamination: An Alarming Threat
to Environment and Human Health....................................................... 103
Sandhya Mishra, Ram Naresh Bharagava, Nandkishor More,
Ashutosh Yadav, Surabhi Zainith, Sujata Mani, and Pankaj
Chowdhary
Part II Sustainable Agriculture
6 Plant Growth-Promoting Rhizobacteria: Diversity
and Applications....................................................................................... 129
Maya Verma, Jitendra Mishra, and Naveen Kumar Arora
7 Plausible Role of Plant Growth-Promoting Rhizobacteria
in Future Climatic Scenario.................................................................... 175
R. Z. Sayyed, N. Ilyas, B. Tabassum, A. Hashem, E. F. Abd_Allah,
and H. P. Jadhav
8 Plant Growth-Promoting Microbes: Contribution
to Stress Management in Plant Hosts..................................................... 199
Krishna Sundari Sattiraju, Srishti Kotiyal, Asmita Arora,
and Mahima Maheshwari
9 Chemistry, Therapeutic Attributes, and Biological
Activities of Dillenia indica Linn............................................................ 237
Ashok K. Singh and Sudipta Saha
Part III Aquatics and Wastewater Treatment
10 Implication of Algal Microbiology for Wastewater
Treatment and Bioenergy Production.................................................... 263
Vinayak V. Pathak, Shamshad Ahmad, and Richa Kothari
11 Efficiency of Constructed Wetland Microcosms (CWMs)
for the Treatment of Domestic Wastewater Using Aquatic
Macrophytes............................................................................................. 287
Saroj Kumar and Venkatesh Dutta
12 Modelling Water Temperature’s Sensitivity to Atmospheric
Warming and River Flow........................................................................ 309
Shaik Rehana, Francisco Munoz-Arriola, Daniel A. Rico, and
Shannon L. Bartelt-Hunt
Part IV Other Aspects
13 Thermophiles vs. Psychrophiles: Cues from Microbes
for Sustainable Industries....................................................................... 323
Monica Sharma
14 Role of Solar Energy Applications for Environmental
Sustainability............................................................................................ 341
Atin K. Pathak, Kapil Chopra, Har Mohan Singh, V. V. Tyagi,
Richa Kothari, Sanjeev Anand, and A. K. Pandey
15 Natural Sensitizers and Their Applications
in Dye-Sensitized Solar Cell.................................................................... 375
A. K. Pandey, Muhammad Shakeel Ahmad,
Nasrudin Abd Rahim, V. V. Tyagi, and R. Saidur
Chapter 9
Chemistry, Therapeutic Attributes, and Biological Activities of Dillenia indica Linn
Ashok K. Singh and Sudipta Saha
Contents
Introduction 238
Chemistry 239
Traditional and Therapeutic Uses 243
Biological Activities of D. indica 245
Cytotoxicity 245
Immunomodulatory 246
Antidiabetic Activity 246
Anti-inflammatory and Antinociceptive Activity 247
Antioxidant Activity 248
Antimicrobial Activity 249
Antidiarrheal Activity 250
Antiprotozoal Activity 251
Antimutagenic Activity 251
Anticholinergic Activity 251
Protoscolicidal Activity 251
Hemolytic Activity 252
Hair Treatment Activity 252
Enzyme Inhibitory Activity 252
Toxicology of D. indica 252
D. indica in Drug Formulation and Drug Delivery 253
Future Prospects 254
Conclusion 254
References 255
Abstract Dillenia indica Linn. (Dilleniaceae) is generally known as elephant apple and locally known as outenga. The vernacular names are chalta, chulta, bhavya, karambel, ouu, and ramphal. This evergreen deciduous tree is markedly disseminated in the seasonal tropics of many Asian countries, in India from Himalaya to south India. The different parts of this plant have been prevalently investigated for the plethora of biological activities including anticancer, antidiabetic, antihyperlipidemic, antileukemic, antioxidant, antimutagenic, antimicrobial, antinociceptive, antidiarrheal, and hairweaving activities. Differently prepared extracts of this plant have been reported mainly to contain a wide range of flavonoids, triterpenoids (lupene-type), phytosteroids, phenolics, alcohols, and ketones and an anthraquinone. Several phytochemical investigations revealed substantial presence of various types of active constituents including β-sitosterol, stigmasterol, betulin, betulinic acid, kaempferol, myricetin, quercetin, dillenetin and rhamnetin. Among these the major chemical constituents are betulin and betulinic acid (lupene-type triterpenoids) that show a wide spectrum of pharmacological activities like anti-HIV, anticancer, antimalarial, anti-inflammatory, etc. The present chapter thus approaches to highlight on phytochemistry, traditional and therapeutic uses, and biological activities of Dillenia indica.
Keywords Dillenia indica · Therapeutic attributes · Phytochemistry · Therapeutic
uses · Pharmacology
Introduction
A vast amount of knowledge and practices on herbal medicinal systems have been transmitted through the ages. For centuries, medicinal plants were the only resources available for the treatment of several diseases which afflicted humanity (Ozdemir and Alpınar 2015). Numerous of these plants are uncommon, endemic, and found only in forest region. There is neither biological data nor satisfactory information that prompted their rarity in the natural surroundings (Kerrigan et al. 2011). Correspondingly, there are many plant species which have been utilized by tribal and folk communities of different forest regions of India; however, their medicinal and also pharmacological esteem is yet obscure as these plants are hardly available. There are many plant species which have been utilized by tribal groups of India; however, their restorative and also pharmacological knowledge is yet obscure as these plants are not easily accessible and studied. Among these, there are few plants belonging to family Dilleniaceae which have not gained much popularity but have interesting medicinal values. The genus Dillenia has 60 species; however, only a few of them are reported to have important phytochemicals and thereby enrich their medicinal values. These species are D. indica, D. pentagyna, D. suffruticosa, D. andamanica, D. serrata, D. sumatrana, D. aurea, D. bracteata, D. excelsa, D. ovata, D. papuana, D. parviflora, D. philippinensis, D. pulchella, D. reticulata, D. scabrella, D. eximia, and D. triquetra. Only two plants D. indica Linn. and D. pentagyna Roxb. are available in India. D. indica has been extensively studied and a more commonly employed medicinal plant in different parts of India (Dickison 1979). Several research works have been conducted on the isolation and quantification of the different phytochemicals from various parts of D. indica; however, very few phytochemical investigations have been performed from D. pentagyna.
Chemistry
The significant classes of chemical constituents extracted from D. indica are flavonoids and triterpenoids (lupene-type). Other isolated compounds including phytosteroids, diterpene, ionone, phenolics, anthraquinone, alcohols, and ketones also enhance the diversity of phytochemistry in D. indica. As per our extensive search, a total of 34 compounds isolated from D. indica are included in this review which may lead to further research and noble challenge to discover new chemical constituents from this plant. These compounds are listed in Table 9.1, and their chemical structures are displayed in Fig. 9.1.
Stem bark of D. indica contains triterpenoids like lupeol, betunaldehyde, and betulinic acid; flavonoids like kaempferol, dillenetin, rhamnetin, dihydro-isorhamnetin, myricetin, naringenin, and quercetin; and 10% tannin (Shah 1978; Khanum et al. 2007; Khare 2007). The ethanol extract of stem bark is enriched with two flavonoids, kaempferol and quercetin, as well as a triterpenoid (Srivastava and Pande 1981). Parvinet al. (2009) acquired methanolic extract of stem after partitioning with n-hexane and isolated four compounds, viz., lupeol, betulinic acid, betunaldehyde, and stigmasterol, using column chromatographic separation.
Leaves of D. indica contain betulinic acid, betulin, lupeol, and β-sitosterol (Dan and Dan 1980). The petroleum ether extract of leaves contains betulin, β-sitosterol, cycloartenone, and n-hentriacontanol, whereas chloroform extract has betulinic acid (Mukherjee and Badruddoza 1981). Methanolic extract of leaves after fractionation with n-hexane and chloroform also has compounds like betulinic acid, β-sitosterol, dillenetin, and stigmasterol (Muhit et al. 2010). Phytochemicals have also been investigated from acid hydrolyzed extracts of dried leaves which demonstrated the presence of kaempferol, whereas fresh leaves were found to contain dihydrokaempferide and naringenin-7-diglucoside which get further oxidized to ten corresponding flavonols (Bate-Smith and Harborne 1971). Kumar et al. (2010) isolated and quantified betulinic acid using validated HPLC method from various fractions such as methanol, ethyl acetate, n-butanol, and water. The highest concentration among them was found in ethyl acetate fraction.
Fruit of D. indica contains about 34% of total phenolics in methanolic extract (Abdille et al. 2005), isorhamnetin (Pavanasasivam and Sultanbawa 1975a), lupeol, betulin, β-sitosterol (Sundararamaiah et al. 1976), and polysaccharide like arabinogalactan. Uppalapati and Rao (1980) reported the presence of steroids, saponins, fixed oil, free amino acids, glycosides, tannins, and sugars in the seeds of D. indica. These scientific reports collectively revealed that betulin, betulinic acid, and β-sitosterol are present in almost all parts of D. indica.
Table 9.1 Compounds isolated from D. indica
 |
| Fig. 9.1 Structure of compounds isolated from Dillenia indica |
Traditional and Therapeutic Uses
Usually all parts of D. indica are traditionally exploited for therapeutic purposes. The jelly-like content inside the fruit of D. indica is applied for hair treatment against dandruff and falling hair. The mixed juices of leaves and stem bark are used orally for the prevention of diarrhea and cancer (Yeshwante et al. 2009a, b; Sunil et al. 2011). The leaves and stem bark are also used as laxative and astringent (Sharma et al. 2009). Apart from this, the stem bark is used for the production of charcoal. The fresh and dried materials of various parts of D. indica are processed as juice, decoction, poultice, and mucilage for the medical care of diabetes, wounds, diarrhea, cancer, rheumatism, urinary problems, skin diseases, aches, fever, cough, and falling hair. Almost all the known medicinal uses of D. indica are enlisted in Table 9.2. Skin diseases including leukoderma, eczema, skin itches, and skin rash can be treated using the leaf, fruit, and stem bark of D. indica (Quattrocchi 2012; Boer et al. 2012; Bhat et al. 2014). Leaves of D. indica as well as decoction and juice of the fruit and stem bark are exploited in daily practices to attenuate cancerous growth, particularly breast and gastric cancers (Das et al. 2009; Sharma et al. 2001). Furthermore, fruit juice of D. indica is supplemented orally to eliminate fever and cough-associated symptoms (Angami et al. 2006; Quattrocchi 2012). The mixed juice of fruit and calyx of D. indica is used in daily practices for the treatment of diabetes (Pavani et al. 2012; Ripunjoy 2013). The root of D. indica is generally utilized for the purpose of abortion (Quattrocchi 2012). Moreover, the mucilage of D. indica fruits is used to treat falling hair, to clean hair, as well as to remove dandruff from hair (Saikia et al. 2006). The sweetish-sour edible fruits of this plant may be consumed directly or juiced with sugar to take as fresh and healthy drink. An interesting event is that the bark of the stem and roots has extensively been used as a food-poisoning neutralizer (Grosvenor et al. 1995a, b; Islam et al. 2014). Altogether, it is concluded that D. indica contains the chemical constituents that can treat a broad spectrum of human ailments.
Table 9.2 Traditional and therapeutic uses of D. indica
Biological Activities of D. indica
Cytotoxicity
Cytotoxic activity of phytochemicals present in different parts of D. indica was screened against numerous cancer cell lines. In vitro cytotoxic activity against leukemia, carcinoma, and lymphoma cells was reported using methanol extracts of D. indica fruit (Kumar et al. 2010) and leaves (Akter et al. 2014). In particular, the methanol extract of the fruit inhibited the growth of U937, HL60, and K562 cancer cell lines with IC50 of 328.80, 297.69, and 275.40 mg/mL, respectively, comparable to standard drugs Ara C and Gleevec (Kumar et al. 2010), whereas the methanol extract of the leaves inhibited the growth of AGS, MCF-7, and MDA-MB-231 cancer cell lines with IC50 values of 1.18, 0.34, and 0.54 mg/mL, respectively, as compared to cycloheximide with IC50 values of 0.0010, 0.061, and 0.0004 mg/mL, respectively (Akter et al. 2014). On the contrary, the ethanol and aqueous extracts were noticed noncytotoxic toward the cancer cell lines (Nguyen-Pouplin et al. 2007; Armania et al. 2013a, b). Ultimately, a significant correlation was established between the presence of betulinic acid and cytotoxic activity of extracts and fractions of D. indica. For example, the ethyl acetate fraction of the methanol extract of D. indica calyx containing considerable amounts of betulinic acid exhibited prominent cytotoxicity when compared to the n-butanol fraction (Kumar et al. 2010). Other than betulinic acid, three compounds (lupeol, betulin, and gallic acid) isolated from D. indica were also proven to have cytotoxic activity toward cancer cell lines. Finally, the result revealed that lupane-type triterpenoids isolated from D. indica (lupeol, betulin, and betulinic acid) displayed considerable cytotoxic properties. Although the cytotoxicity of this plant is very less studied and needs to be performed on variety of cell lines, however, these findings may provide a great opportunity for further development of anticancer compounds from D. indica.
Immunomodulatory
The cornerstone of good health is no doubt a strong, well-functioning immune system. Phytochemicals such as flavonoids, terpenoids, glycosides, and phenolic compounds act as a natural defense system not only for the host plant, but also they can serve in immunomodulatory activities in humans (Venkatalakshmi et al. 2016). For example, the aqueous methanolic extract (70%) of D. indica fruit enhanced the production of polyclonal immunoglobulin M (IgM) in cultured BALB/c female mice spleen cells at a concentration of 200 mg/mL as compared to lipopolysaccharide (0.1 mg/mL) (Sarker et al. 2012).
Antidiabetic Activity
Indian natives have since long used D. indica to treat diabetes. The leaf extract of D. indica was found to inhibit enzymatic activity of rat intestinal sucrose and maltase (Jong-Anurakkun et al. 2007). Moreover, the leaf extract of D. indica assayed on streptozotocin (STZ)- and alloxan-induced type 1 and type 2 diabetic rats reduced the levels of blood glucose, hypertriglyceridemia, and hypercholesterolemia. In fact, the extract enhanced the production of insulin and high-density lipoprotein cholesterol (HDL-c) (Jong-Anurakkun et al. 2007; Kumar et al. 2011a, b). Additionally, the extract inhibited overproduction of liver function enzymes such as aspartate transaminase (AST), alanin transaminase (ALT), and alkaline phosphatase (ALP) in diabetic rats (Kumar et al. 2011a, b). Histopathological studies showed that the liver, pancreas, and kidney in the treated rats restored to normal conditions after treatment with the extract of D. indica (Kumar et al. 2011b). In an experiment performed by Kumar et al. (2011a, b), the ethyl acetate fraction of the methanol extract of the leaves assayed in vivo on STZ-induced type 1 and type 2 diabetic rats showed a reduction in blood glucose, serum cholesterol, and triglyceride levels after 21 days of treatment at the doses of 200 and 400 mg/kg body weight (bw). This fraction also increased the level of HDL-C in the treated rats. Likewise, the defatted methanol extract of the leaves assayed in vivo on type 1 diabetic rats induced by STZ and alloxan decreased the blood glucose, hypertriglyceridemia, and hypercholesterolemia levels as well as increased the production of insulin and HDL-C at the doses of 250 and 500 mg/kg bw during 21 days of treatment (Jong-Anurakkun et al. 2007; Kumar et al. 2011a, b). In another experiment, three compounds (quercetin, β-sitosterol, and stigmasterol) isolated from the ethyl acetate fraction of this extract were found to reduce the blood glucose level of type 2 STZ-nicotinamide-induced diabetic mice which was comparable to standard drug glibenclamide (Kumar et al. 2013). Later, similar activity was performed by the extract of D. indica fresh leaves assayed on STZ-induced diabetic rats. Further investigation of active constituent of this extract led to the isolation of 3,5,7-trihydroxy-2-(4-hydroxy-benzyl)-chroman-4-one, which significantly demonstrated antidiabetic activity by reducing blood glucose, cholesterol, and triglycerides levels. The treatment also increased the levels of insulin, HDL-C, as well as body weight when compared with diabetic rats. Histopathological study showed that treatment with the extract and 3,5,7-Trihydroxy-2-(4-hydroxy-benzyl)-chroman-4-one restored the hyperglycemic conditions and kidney structure abnormality owing to oxidative stress in the diabetic rats (Kaur et al. 2016). The alcoholic extract of the fresh leaves assayed in vivo on STZ-induced diabetic rats reduced levels of blood glucose, cholesterol, and triglycerides at doses of 100, 200, and 400 mg/kg bw for 21 days of treatment, comparable to glimepiride (10 mg/kg bw). The extract significantly increased the body weight, serum insulin and HDL-C levels (Kaur et al. 2016). These findings well supported the traditional use of D. indica for the treatment of diabetes among Indian natives.
Anti-inflammatory and Antinociceptive Activity
Many of D. indica extracts were tested for anti-inflammatory and antinociceptive activities. The alcoholic extract of D. indica leaves obliterated carrageenan-induced paw edema at doses of 200 and 400 mg/kg bw with the impact comparable to indomethacin (10 mg/kg bw) (Yeshwante et al. 2009a, b). Moreover, the methanol extract of the leaves and its nonpolar fractions assayed on acetic acid-induced colitis mice at doses of 200 and 800 mg/kg bw restored the colon weight and macroscopic damage in acetic acid-induced colitis in mice. The non-polar fractions also attenuated the production of tumor necrosis factor alpha (TNF-α) and myeloperoxidase released from azurophilic granules of neutrophils (Somani et al. 2014). On the other hand, the glycolic extract and emulsion of D. indica fruit were not found suitable to accelerate wound healing process on skin injuries made in rats (Miglianto et al. 2011). The alcoholic extracts of the leaf and stem bark of D. indica were examined for antinociceptive activity using the hot plate method, tail immersion test, and writhing model in mice induced by acetic acid and found to exhibit central and peripheral analgesia (Bose et al. 2010; Yeshwante et al. 2011; Alam et al. 2012). In particular, the methanol extract of the leaves was evaluated on acetic acid-induced writhing mice at doses of 250 and 500 mg/kg bw which obliterated the writhing behavior by 48.82% and 55.88% inhibition comparable to that of diclofenac (60% at 25 mg/kg bw) (Bose et al. 2010). Furthermore, the methanol extract of the leaves measured by hot tail, tail immersion, formalin-induced nociception, and acetic acid-induced writhing model on mice at doses of 400 mg/kg bw considerably exhibited central and peripheral analgesia when comparable to those of the standard drugs, pentazocine (15 mg/kg bw) and indomethacin (20 mg/kg bw) (Yeshwante et al. 2011). Later, the methanol extract of the stem bark was evaluated using hot plate method, tail immersion test, and acetic acid-induced writhing model in mice at doses of 200 and 400 mg/kg bw that demonstrated dose-dependent analgesic activity comparable to those of the standard drugs nalbuphine (10 mg/kg bw) and diclofenac sodium (10 mg/kg bw) (Alam et al. 2012).
Antioxidant Activity
Flavonoids, terpenoids, tannins, and phenolics in D. indica plants are major compounds responsible for primary antioxidants or free radical scavenging effects (Polterai 1997). A compound 3,5,7-trihydroxy-2-(4-hydroxy-benzyl)-chroman-4-one isolated from D. indica displayed remarkable antioxidant property when assayed on 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), hydrogen peroxide, and superoxide radicals as well as ferric ion. This compound also elevated the production of antioxidant enzymes (superoxide dismutase and glutathione) in streptozocin (STZ)-induced diabetic rats. Treatment with this compound remarkably reduced the level of lipid peroxidation marker, i.e., thiobarbituric acid-reactive substances (TBARS) in diabetic rats (Kaur et al. 2016). In an experiment, methanol, ethyl acetate, and aqueous extracts of the fruit reduced molybdenum (IV) to molybdenum (V) with the capacity of 1904.80, 1067.00, and 594.60 mmol/g of extract, respectively, when compared to ascorbic acid. The extracts also exhibited DPPH free radical scavenging activity over the concentration range of 25–100 mg/mL with the activity in order of methanol extract > ethyl acetate extract > water extract. The extracts when evaluated on β-carotene bleaching produced antioxidant activity with the capacity of 80.20, 55.50, and 45.50%, respectively, at 100 mg/mL when compared to BHA (97.50%) (Abdille et al. 2005). In another experiment, the aqueous acetone extract of the stem bark reduced molybdenum (IV) to molybdenum (V) with capacity of 3.12 mmol/g of extract at 50 mg/mL as compared to ascorbic acid and exhibited DPPH and superoxide radical scavenging activity causing 90.90% and 31.73% inhibition at 25 and 50 mg/mL which were found to be comparable of BHA (91.00%) and gallic acid (47.73%), respectively. The extract also assayed using hydroxyl radical-induced deoxyribose damage which showed radical scavenging activity with percentage inhibition of 53.90–74.66% at 100–500 mg/mL (Deepa and Jena 2011). Furthermore, the ethanol extract of the leaves assayed in vitro by DPPH, hydroxyl, and hydrogen peroxide radicals displayed antioxidant activity with IC50 of 34.80, 64.40, and 51.00 mg/mL, respectively, as compared to ascorbic acid with IC50 of 24.00, 48.00, and 34.40 mg/mL, respectively. The extract also measured using ferric-reducing antioxidant power (FRAP) assay caused the reduction of ferric ion as compared with ascorbic acid (Shendge et al. 2011). Later, similar extract also evaluated in vivo on doxorubicin-induced rats that restored the levels of GSH and cardiac malondialdehyde (MDA) at doses of 250 and 500 mg/kg bw (Shendge and Gadge 2012). In another experiment on Swiss albino mice, the methanol extract of the stem bark reduced the production of ROS in kidney cells with IC50 of 34.72 mg/mL as compared to trolox (IC50 8.66 mg/mL) (Alam et al. 2012). Further, Singh et al. (2012) also demonstrated that methanol, acetone, and water extracts of the stem bark measured by DPPH radical produced antioxidant activity with IC50 values of 188.08, 177.42, and 163.68 mg/mL of fresh mass, respectively. It was also investigated that the methanol extract of the leaves and its nonpolar fractions reduced the level of MDA and, however, enhanced the levels of the antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) in acetic acid-induced colitis at doses of 200 and 800 mg/kg (Somani et al. 2014). Interestingly, a compound proanthocyanidins isolated from D. indica fresh fruit produced significant antioxidant activity measured by FRAP and oxygen radical absorbance capacity (ORAC) assays with values of 2.32 × 103 mmol Fe(II)/g and 1.06 × 104mmol trolox equivalent/g (Fu et al. 2015). Lastly, the alcoholic extract of the fresh leaves obtained from sequential extraction with petroleum ether, chloroform, alcohol, and aqueous alcohol (40%) exhibited free radical scavenging activity toward DPPH, hydrogen peroxide, and superoxide radicals with IC50 of 2.98, 228.69, and 75.09 mg/mL, respectively, and ferric-reducing antioxidant power with EC50 of 111 mg/mL. In the similar experiment, it was also investigated that the extract enhanced the production of antioxidant enzymes (SOD and GSH) in STZ-induced diabetic rats at doses of 100, 200, and 400 mg/kg bw after 21 days of treatment when compared to glimepiride at 10 mg/kg bw (Kaur et al. 2016).
Antimicrobial Activity
D. indica was investigated for antibacterial, antifungal, and antiviral activities. The extracts and fractions of D. indica were documented to show growth inhibition against Gram-positive and Gram-negative bacteria. However, in comparison to bacteria, they attenuated the fungi including Aspergillus fumigatus, Aspergillus niger, Penicillium sp., Candida albicans, Candida krusei, Rhizopus oryzae, Saccharomyces cerevisiae, and Trichoderma viride (Nick et al. 1995a, b; Wiart et al. 2004; Haque et al. 2008; Apu et al. 2010; Smitha et al. 2012). Betulinic acid isolated from D. indica has proven antimicrobial activity (Nick et al. 1994, 1995a, b; Ragasa et al. 2009). Meanwhile, a few nonpolar fractions (chloroform, carbon tetrachloride, and hexane) of the methanol extract of the leaves weakened the growth of Escherichia coli, Bacillus cereus, Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Sarcina lutea, Pseudomonas aeruginosa, Vibrio mimicus, Vibrio parahemolyticus, Salmonella typhi, Salmonella paratyphi, Shigella boydii, and Shigella dysenteriae and fungal inhibition of A. niger, C. albicans, and S. cerevisiae with inhibition zones ranging from 6 to 8 mm at 400 mg/disc when compared with kanamycin (30 mg/disc; 30–40 mm) (Apu et al. 2010). In another experiment, hexane, dichloromethane, and ethyl acetate fractions of the methanol extract of the stem bark inhibited the growth of E. coli, B. cereus, B. subtilis, S. aureus, S. lutea, P. aeruginosa, V. mimicus, V. parahemolyticus, S. paratyphi, S. typhi, and S. dysenteriae with minimum inhibitory concentration (MIC) ranging from 0.31 to 20.00 mg/mL as compared to those of kanamycin (30 mg/disc; 22–30 mm) and amoxicillin (10 mg/disc; 14–22 mm). These fractions also attenuated the growth of A. niger, C. albicans, and S. cerevisiae with the inhibitory zones ranging from 7 to 13 mm as compared to ketoconazole (50 mg/disc; 19–23 mm) (Alam et al. 2011). Jaiswal et al. (2014) concluded that the aqueous acetone (70%) extract of the fruit and stem bark inhibited the growth of food-borne pathogens (B. cereus, S. aureus, Yersinia enterocolitica, and E. coli) with minimum inhibitory concentration ranging from 1.25 to 10.00 mg/mL. These findings suggest that D. indica has a powerful potential as antimicrobial agent, which supports it as traditional therapeutic remedy against the diseases caused by microbial infection, like diarrhea, dysentery, septicemia, and skin diseases.
Antidiarrheal Activity
In an experiment, castor oil-induced mice were used to check the antidiarrheal activity of D. indica. The aqueous and methanolic extracts of the leaves prolonged the onset and reduced the total number of feces after 2 h of treatment at doses of 200 and 400 mg/kg bw (Yeshwante et al. 2009a, b). The polar extracts of the leaf and fruit caused the prolongation of onset and curtailment in defecation frequency in the treated mice. The assay of extracts using charcoal meal revealed that it had a capacity to reduce the motility of the gastrointestinal tract (Yeshwante et al. 2009a, b; Bose et al. 2010; Rahman et al. 2011a, b). Further, the methanol extract of the leaves significantly diminished the frequency of defecation and number of total stool count at a dose of 500 mg/kg bw as compared to loperamide (25 mg/kg bw; 77.22%) (Bose et al. 2010). Ethanol extracts of the fruit and leaves minimized the total number of wet feces and also decreased the motility of gastrointestinal tract in castor oil-induced diarrheal mice at doses of 200 and 400 mg/kg bw when compared with loperamide (5 mg/kg bw) (Rahman et al. 2011b). The antidiarrheal action of this plant is suggested due to inhibition of inflammatory mediators by flavonoids and tannins (Yeshwante et al. 2009a, b).
Antiprotozoal Activity
Antiprotozoal activities of D. indica against malaria and leishmaniasis have been tested. Cyclohexane fraction of ethanolic extract of D. indica leaves was reported to inhibit the growth of parasite Plasmodium falciparum. In this experiment, cyclohexane fraction of the 80% ethanol extract of the leaves exhibited 53% inhibition against parasite P. falciparum at a concentration of 10 mg/mL as compared to chloroquione (Nguyen-Pouplin et al. 2007).
Antimutagenic Activity
Mutations are the cause of innate metabolic defects in cellular mechanism which trigger initiation and progression of several human diseases including cancer. The antimutagenic and protective effect has been ascribed to many classes of phytochemicals preferably flavanoids and phenolic compounds (Aqil et al. 2008). Meanwhile, Jaiswal et al. (2014) found that 70% aqueous acetone extract of the stem bark of D. indica demonstrated antimutagenic activity against sodium azide-induced mutation in Salmonella tester strain (TA-1531).
Anticholinergic Activity
Anticholinergics generally inhibit the action of acetylcholine from binding to its receptor sites on certain nerve cells and block parasympathetic nerve impulses. Bhadra et al. (2014) found that the standardized methanol extract of the fruit of D. indica inhibited acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) activity with IC50 values of 67.26 and 122.39 mg/mL, respectively.
Protoscolicidal Activity
The scolicidal agents are generally employed in surgical manipulation of the hydatid cysts in hydatid diseases (García et al. 1997). Chowdhury et al. (2013) investigated the protoscolicidal activity in the stem bark of D. indica where an assay of the methanolic extract of the stem of D. indica was performed on earthworm Pheretima posthuma, and the result demonstrated the paralysis (194–136 min) and death (237–176 min) of the worms at 10–25 mg/mL comparable to albendazole at 10 mg/mL.
Hemolytic Activity
Hemolytic activity of any compounds is a measure of general cytotoxicity toward normal healthy cells (Da Silva et al. 2004). This activity was investigated by Jaiswal et al. (2014) in D. indica plant where the aqueous acetone (70%) extract of the fruit and stem bark of D. indica was assayed using rat whole blood which exhibited low inhibition against erythrocytes.
Hair Treatment Activity
On the basis of the previous information that keratin is the main component and mechanical strength of the hair, an experiment was performed where the aqueous extract of the mucilaginous D. indica seed sap protected human hair from loss of keratin after treatment with 10 mg hair/1 mL for 12 h. The physical structure of hair and keratin degradation were further affirmed by Fourier transform infrared spezctroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy
(SEM) analysis, and a good hair weaving activity was noticed (Saikia 2013).
Enzyme Inhibitory Activity
Inhibition is one major mechanism for physiological enzyme regulation. Further, enzyme inhibition has a number of medicinal significances, and a large number of drugs generally act by the mechanism involving enzyme inhibition. In this view Jong-Anurakkun et al. (2007) performed an experiment to assure whether D. indica has an enzyme inhibitory action. As a result, the 50% aqueous methanolic extract of the leaves attenuated the intestinal sucrose and maltase activity with percentage inhibition of 40% and 56%, respectively.
Toxicology of D. indica
Several types of extracts of D. indica were tested for their toxicity action against Artemia salina. Despite the toxicity, some extracts of D. indica were found nontoxic (Kumar et al. 2010) and exhibited ameliorative (Shendge and Gadge 2012) and hepatoprotective (Padhya et al. 2008; Himakar et al. 2010) actions when assayed using in vivo models. The ethanolic extract of the leaves restored the level of myocardial enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CK) on myocardium of doxorubicin-induced rats at doses of 250 and 500 mg/kg bw (Shendge and Gadge 2012). However, the ethanolic extract of the leaves reduced the levels of serum AST, ALT, ALP, bilirubin, and lipid peroxidation in the the liver induced by carbon tetrachloride at a dose of 300 mg/kg bw (Padhya et al. 2008). The nonpolar hexane extract of the seeds decreased the levels of serum enzymes, bilirubin, urea, creatinine, and lipid peroxidation but increased the levels of SOD,CAT, glutathione reductase (GR),
glutathione peroxidase (GPx), and glutathione S-transferase (GST) in CCl4-induced rats at doses of 250 and 500 mg/kg bw (Himakar et al. 2010). Besides these, D. indica has been used as food poisoning neutralizer (Islam et al. 2014; Grosvenor et al. 1995a, b) which also evidenced that D. indica is safe and not toxic. The methanolic extract of the leaves was nontoxic and did not produce any mortality in mice during 24 h of treatment with 100–1500 mg/kg bw of extract by intraperitoneal
administration (Kumar et al. 2010). Apart from this, water, chloroform, carbon tetrachloride, and n-hexane fractions of methanol extract of the leaves demonstrated lethality on brine shrimp as compared to vincristine sulfate (Apu et al. 2010). However, the methanol, ethyl acetate, dichloromethane, and n-hexane extracts of the stem bark exhibited inhibition on brine shrimp with less lethality when compared to the leaf extracts (Parvin et al. 2009; Alam et al. 2011; Chowdhury et al. 2013).
D. indica in Drug Formulation and Drug Delivery
The mucilage obtained from seeds of D. indica fruit contains a natural mucoadhesive hydrophilic polymer, which is generally used in the formulation for drug delivery (Sharma et al. 2009; Bal et al. 2012a, b). The mucoadhesive and viscous properties of mucilage of D. indica fruit were used as better substitute of synthetic polymers, i.e., Carbopol 934 (Kuotsu and Bandyopadhyay 2007; Bal et al. 2012b) and hydroxylpropyl methyl cellulose. Novel mucoadhesive buccal tablets of oxytocin and formulation of nasal gels were prepared from D. indica (Kuotsu and Bandyopadhyay 2007; Metia and Bandyopadhyay 2008). Bal et al. (2012a, b) developed a mucoadhesive carvedilol microcapsule using the mucilage obtained from seeds of D. indica for encapsulation purpose. This microcapsule was found to be free flowing and usually spherical in shape. It was concluded that this mucilage was effective for sustained drug release, which can be employed to reduce the hypertension for a period of 24 h. Further, Sharma et al. (2013) conducted an experiment where they encapsulated pantoprazole sodium and metformin hydrochloride, respectively, using this mucilage. Good swelling properties and mucoadhesivity was found to perform at the intestinal pH. This finding suggested that the seed mucilage of D. indica has good potency for the purpose of drug encapsulation (Sharma et al. 2010). Nanoparticles are being extensively used as drug carrier for the treatment of diseases nowadays. Singh et al. (2013) prepared colloidal silver nanoparticles (SNP) using the aqueous extract of D. indica fruits as reducing agent and as a better substitute of sodium borohydride. This extract reduced AgNO3 to silver nanoparticles with stability more than 6 days, which suggested that D. indica could be employed as natural reducing agent for silver nanoparticles loaded formulation.
Future Prospects
Despite a broad range of medicinal properties of D. indica, very few investigations regarding chemical constituents and pharmacological aspects have been carried out. There is little evidence over the quantification of different active phytoconstituents responsible for important pharmacological activities. It is evident from the available literature that D. indica possesses adequate therapeutic potential and need to be explored further for chemical and pharmacological investigations. Current knowledge of D. indica shows great lacunae that need more biological investigations to be done on its plant extracts. Hence, further studies are highly required to explore the potential of its plant extracts against various diseases and search for molecular mechanisms underlying their action. Future studies are also required to evaluate the adverse effects, safety profile, and different biological activities of extracts as well as particular chemical constituents from D. indica in order to facilitate their clinical applications as modern medicines for human health.
Conclusion
Herbal medicines are the most extensively used therapeutics worldwide. To promote their proper use and to establish their potential as sources for new drugs, it is necessary to study medicinal plants having folklore reputation in a better and intensified way. The extensive literature survey as well as research reports revealed that D. indica is highly regarded to have good potential in the herbal medicine. Betulin and betulinic acid are the major constituents found to be present in almost all parts of this plant which can cure various human ailments and diseases. As the raw fruits are eaten by tribal communities, the juice of D. indica may be taken as energy drink due to their good nutritional value. It has previously been confirmed that D. indica have curing properties in wound healing, diabetes, cuts and burns, abdominal pains, and many more, but scientific evidence of these reports is yet not much developed. Various pharmacological investigations have been done using different plant parts such as leaves which have various activities like antioxidant, cytotoxic, antimicrobial, antidiarrheal, and anxiolytic, seeds which are hepatoprotective and antimicrobial, and fruits which are antileukemic. Despite a few toxicity reports, D. indica and most of its extracts were found to be non-toxic and exhibited ameliorative and hepatoprotective activities in several in vivo studies. The ethnopharmacological use of D. indica as food poisoning neutralizer also indicates its better safety profile and non-toxic nature. The current status of D. indica demands some biotechnological investigations including protein and gene expression for target identification and exploration of molecular mechanisms underlying the action at molecular levels.
Acknowledgments The authors are grateful to the Vice Chancellor of Babasaheb Bhimrao
Ambedkar University, Lucknow, India, for the support.
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