INTRODUCTION:

The importance of good nutrition to good health has long been appreciated worldwide. Good nutrition is important mainly for growth, health and immunity. There is a triad between nutrition, immunity and infection and the absolute intake of multiple nutrients have an influence on susceptibility to infection and host immune response and possibly on susceptibility and treatment of autoimmune disorders¹. There several complex factors that affect the relationship of nutrition and immunity, including the heterogeneity of the food we eat, our differing abilities to handle various nutrients and the influence of environment on specific nutritional needs². Infection and malnutrition have always been interconnected³. Malnutrition is one of the major leading causes of the immunodeficiency worldwide.

Micro- as well as macronutrient deficiencies have effects such as poor growth, impaired intellect, and increased mortality and susceptibility to infection⁴. Infectious diseases are the other major cause of morbidity and mortality worldwide. Several antimicrobial remedies such as antiviral, antibacterial, antifungal, anthelmintics and antibiotics drugs have been widely used for treatment of various pathogenic infectious diseases⁵. Due to alarming increase in continuous and indiscriminate use of various synthetic antibiotics the pathogenic microbial strains have developed a number of multidrug-resistant microbial strains with reduced vulnerability to antibiotics. Moreover, most of the synthetic drugs produce multiple adverse effects including biochemical and metabolic alterations. Thus, a need arises for newer and safer antimicrobial agents efficient in controlling multidrug-resistant microbial infections with minimal adverse effects⁶. Chronic infectious and inflammatory conditions have been linked to carcinogenesis and metastatic processes of cancer in recent research, and the involvement of inflammatory reactions in the development of neoplasia has also been reported⁷. Cancer being one of the frequent causes of death worldwide is a cohort of diseases with uncontrolled cell proliferation. Carcinogenesis involves several processes including hyper-proliferation, cellular transformation, angiogenesis, invasion and metastasis. The interplay of multiple inflammatory modulators is required for cancer to proceed from a single cell. The outcome of a cell's malignancy or normal growth is determined by this intricate chain of events⁸. Compounds that can block or change inflammatory reactions offer a lot of promise for cancer management, prevention, and treatment⁹. If medicine could inhibit inflammatory reactions while also inducing death in cancer cells, it could be effective for both cancer prevention and treatment³. Cuscuta reflexa Roxb one of such plants is used traditionally in prevention and treatment of several ailments and has been extensively studied and proved for its several beneficial effects on health and efficacy in treatment of broad spectrum of microbial infections, inflammation, malnutrition and cancer. It has been documented for potent antimicrobial, anti-inflammatory, antioxidant and immunomodulatory properties. It has been studied for its anticancer effects against broad spectrum of cancers in several in vitro and in vivo studies. These studies have exhibited potent anticancer effects of Cuscuta reflexa (C. reflexa) and its phytoconstituents, targeting various molecular pathways involved in cancer initiation and progression^7-19. The present review is a compilation of several preclinical and clinical investigations conducted to explore the anticancer, anti-infective and immunomodulatory efficacy of C. reflexa and its phytoconstituents with special emphasis on molecular targets affected by C. reflexa in eliciting these effects.

Plant Profile of Cuscuta reflexa:

Figure 1. Cuscuta reflexa Roxb (whole plant)

Morphology:

Macroscopic characters:

C. reflexa is made up of a dense tuft of intertwined, heavily branching, nearly thread-like light brown stem mass, as well as portions of the host plant with the stem, twined on it. The stem is rough to the touch, glabrous, without leaves and easily breaks. Fruits are borne on stems in clusters of 5-8 in a single cyme and are light brown. It has no odour and a mildly bitter flavour. Fruit is an indehiscent capsule with a globe shape and a diameter of 3-5mm that is borne on a pedicle. Each fruit contains four seeds. It features a persistent calyx and a very translucent wall that allows the dark brown seeds to be seen plainly. It has a small pore at the top and some bears that are still attached are reminiscent of style (Figure 1)¹⁰.

Microscopic characters:

The stem's transverse section has a round but wavy appearance. A single row of epidermis lines the outermost layer, which is surrounded by a cuticle. The morphology of epidermal cells is not uniform. A 4–6-layer cortical zone with thin-walled cells of diverse sizes and shapes. The endodermal layer is undetectable. The cells in the innermost layer of the cortex shrink and create a sheath around the vascular bundles. Collateral vascular bundles are 5-7 in number and do not share the same radius. The xylem is not well developed and is made up of a single group of thin vessels. Except for certain large cells with little companion cells outside the metaxylem, phloem is difficult to discern. In the center, there is a huge zone of pith with thin-walled cells. The pith cells are brown. Isolated cells have some calcium oxalate prismatic crystals¹⁰.

Synonyms:

Amarvallari, Khavalli, Akashvalli, Asprsha, Aakashbel, Aaloklata, Vyomvallika, Amarbel^10,11.

Habitat:

C. reflexa creeps over trees and plants. It can be found in temperate and tropical climates over the world, with a diverse range of species in tropical and subtropical areas. India, Afghanistan, Sri Lanka, Malaysia, Thailand and Nepal are the most common locations¹¹.

Phytochemistry:

C. reflexa is cultivated on several host plants has yielded a variety of phytoconstituents. Phytochemicals isolated from C. reflexa include flavonoids, dulcitol, mannitol, sitosterol, lycopene, apigenin-7-β-rutinoside, 6-7 dimethoxy coumarin, quercetin, hyperoside, propenamide, reflexin, lutein, carotene, amarbellin, palmitic, oleic, stearic, linolenic acids, luteolin, cuscutin, cuscutalin, kaempferol, kaempferol-3-O-glucoside, astragalin, benzopyrones, glucopyranosides, quercetin-3-O-glucoside, bergenin¹². Cuscutalin (1%) and cuscutin (0.02%) are the two primary active principles found in the plant¹³. Wax and reducing sugars are also present in the plant. Amarvelin, resins, oil (3%) and reducing sugars are all present in the seeds. These constituents vary depending on the host on which the dodder parasitizes. D-mannitol is produced by the Santalum album, while luteolin or kaempferol is produced by Glycomistriphylla and dulcitol is produced by others. Apart from this, two new 2H-pyran-2-one glucosides, cuscutarosides A and B, and one new steroidal glucoside, 7β-methoxy-β-sitosterol 3-O-β-glucopyranoside, together with 12 known compounds were isolated from the whole plant of C. reflexa collected from Myanmar¹⁴.

Pharmacological activities:

C. reflexa has been documented to possess various pharmacological activities such as anticancer¹⁵, anti-inflammatory¹⁶, antibacterial¹⁷, antimicrobial¹⁸, immunomodulatory, anti-asthmatic¹⁹, anti-diabetic²⁰, antidiarrheal, antiemetic²¹ antiepileptic²² antifungal, antiviral²³, antipyretic²⁴, antisteroidogenic²⁵, antimutagenic²⁶ and larvicidal activity²⁷.

Anticancer activity:

Cancer is one of the most dreadful diseases manifested by uncontrolled cell growth and proliferation. The rate of morbidity and mortality rate due to cancer has been continuously increasing worldwide²⁸. Various treatment modalities are being used for the cancer therapy.Cancer chemotherapeutic drugs available in the market are associated with severe adverse effects²⁹. C. reflexa Roxbhas been documented for itsanticanceragainst various types of cancers³⁰.

Melanoma tumor:

Hydroalcoholic extract of C. reflexa at the doses 250 and 500 mg/kg showed anticancer activity against melanoma tumor by B16F10 cell line in the experimental animals. It also prevented cyclophosphamide induced micronucleus formation in these animals at the same doses exhibiting anticarcinogenic activity against melanoma cancer and chemoprotective activity against cyclophosphamide induced micronucleus formation. The flavonoids present in the C. reflexa were attributed for these activities³¹.

Breast cancer:

Antiproliferative activity of whole plantof C. reflexa was explored by Bhagwat et al., 2013, wherein, aqueous, alcoholic and hydro-alcoholic extracts and aqueous, n-hexane, n-butanol and chloroform fractions were investigated for In vitro cytotoxicity and In vivo antitumor activity using mouse model. The results revealed that alcoholic extract and its chloroform fraction exhibited most potent activity against MCF-7 cell lines of human breast cancer. The alcoholic extract (40mg/kg) and its chloroform fraction (10mg/kg) showed marked inhibition of tumor growth against both Sarcoma -180 solid tumor and Ehrlich tumor models. Thus, the study suggested that the alcoholic extract and its chloroform fraction of C. reflexa whole plant interferes with cell proliferation to inhibit cancer^30,32.

Colorectal cancer:

Three phenolic components namely stigmasta-3,5-diene,scoparone and p-coumaric acid and a compound namely 10-hydroxycinnamoylglucose extracted from C. reflexa were explored for anticancer activity in HCT116 cell lines of human colorectal cancer^31,33. The results exhibited that the compound 1-O-p-hydroxycinnamoyldlucose showed marked antiproliferative activity while the three phenolic components showed moderate activity. In a recent study by Mishra et al., 2022, the ethanolic extract of C. reflexa showed potential anti-cancer effects against 1, 2- Dimethyl hydrazine induced colorectal tumours in experimental animals. The activity was assessed through haematological and histopathological parameters, colonoscopy, barium enema X-ray and aberrant crypt foci studies. C. reflexa was found to restore the haematological parameters such as red blood cell counts, haemoglobin content, packed cell volume, mean cell haemoglobin, mean corpuscular volume and mean corpuscular haemoglobin concentrationto the normal levels and the histopathological results revealed that the C. reflexa extract was found to markedly reduce the cell proliferation with no toxicity along with reduction in cancer induced colon damage. C. reflexa extract enhanced the apoptosis and reduced the mitotic bodies in animals bearing DMH induced tumors thus exhibiting potent antitumor activity^34,35.

Ehrlich's ascites carcinoma (EAC):

Chloroform and ethanolic extracts of C. reflexa were tested for antitumor activity against Ehrlich's ascites carcinoma in mice at doses of 200 and 400mg/kg body weight orally. Tumor volume, number of viable and nonviable tumor cells and host haematological characteristics were assessed to determine antitumor activity. Both the chloroform and ethanol extracts of C. reflexa demonstrated strong anticancer efficacy by reducing the viable cell count and tumor volume, restoring the haematological parameters such as haemoglobin content, red blood cells (RBC), white blood cells (WBC) and lymphocyte counts to normal levels and enhancing the life span of the EACtumor-bearing mice. The results were found to be equipotent to the reference standard 5-fluorouracil³⁶.

Anti-inflammatory activity:

Inflammation occurs when bacteria, viruses, or fungi attack the body, infect specific tissues, and/or circulate in the circulation. Tissue injury, cell death, malignancy, ischemia, and degeneration are all causes of inflammation. Both innate immune responses, as well as an adaptive immune response, are involved in the formation of inflammation³⁷. The innate immune system has an elite Défense mechanism against infecting micro-organisms and cancer cells⁵. Inflammatory reactions play a vital role in different phases of the pathogenesis of cancer⁷ hence, there may be a hypothesis that anti-inflammatory drugs can induce apoptosis in cancerous cells⁶. Pro and anti-inflammatory mediators are the most common types of inflammatory chemicals. Interleukin [IL]-12, for example, has both pro-and anti-inflammatory characteristics³⁸. Tumor necrosis factor-α is an important pro-inflammatory cytokine secreted from various cells. Aqueous extract of C. reflexa reduced LPS-induced upregulation of TNF-αand COX-2 in RAW264.7 cells, prevented NF-B binding to its motifs, and increased apoptosis in Hep3B cells, as demonstrated by MTT, DAPI, and annexin V staining studies. The extract increased the levels of pro-apoptotic proteins BAX and p53 while decreasing the levels of anti-apoptotic factors Bcl-2 and surviving (Figure 2)³. Another study results revealed that the alcoholic and aqueous extracts of stems of C. reflexa at the doses of 200 and 400mg/kg b.w. were found to show potential anti-inflammatory activity in carrageenan-induced paw edema model in rats¹⁶. In a similar study, aqueous extract, methanol extract and petroleum ether extract of C. reflexa at three doses i.e. 50, 200 and 300mg/kg was evaluated for anti-inflammatory activity using models like carrageenan, serotonin and histamine-induced paw edema models and cotton pellet induced granuloma model³⁸. Probable mechanism involved in the antiinflammatory effect of methanol and aqueous extracts was evaluated with various tests like ulcerogenicity test; acetic acid induced vascular permeability test and leukocyte migration test using a single dose of 300mg/kg orally. Both methanolic and aqueous extracts at the dose levels of 200 and 300 mg/kg showed potent antiinflammatory activity against carrageenan, serotonin and histamine -induced paw edema. This activity was attributed to the presence of quercetin in mehanolic extract of C. reflexa³⁹.

Figure 2. Mechanism for anticancer and anti-inflammatory activity of Cuscuta reflexa

Antimicrobial activity:

C. reflexa has been found to possess potent antimicrobial activity against various types of microorganisms. Several extracts of various parts of C. reflexa plant have shown promising microbicidal activities against several bacterial species such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, fungal species including Penicillium atrium and Aspergillus niger and viral species such as human immune deficiency virus (HIV). Several phytoconstituents such as alkaloids, carbohydrates, glycosides, flavonoids, tannins, phenolic compounds, steroids and flavonoid glycosides were attributed for antimicrobial properties exhibited by C. reflexa. Antimicrobial activity was found to be more potent in fungi and gram-negative bacteria than in gram-positive bacteria^40-51.

Antibacterial activity:

Antibacterial agents are the agents used to kill bacteria or suppress the growth of bacteria. Several extracts of C. reflexa have shown promising antibacterial activities against several bacterial species. Several phytoconstituents of C. reflexa have been documented to possess potential antibacterial activity^40-44.

Antifungal activity:

Acetone, aqueous, methanolic, ethanolic and butanolic extracts of C. reflexa Roxb. were investigated for antifungal activity against fungal species such as Rhizopus sp., Aspergillus sp., Penicillium sp. and Fusarium sp. Out of these, aqueous, ethanolic and butanol extracts of C. reflexa Roxb. were found to be effective against the Fusarium sp., Aspergillus sp., and Penicillium sp.⁴⁶. C. reflexa extract (a parasite of Bougainvillea glabra L.) was tested In vitro against five different pathogenic fungi, including Alternaria, Aspergillus niger, Fusarium solani, Fusarium oxysporium and Macrophominaphaseolina. C. reflexa in various aqueous concentrations (10, 20 and 30%). Aqueous concentrations of C. reflexa were assessed relative to the fungal isolate by the good diffusion method. The fungitoxicity of the extract was calculated from the diameter of the zone of inhibition. C. reflexa extract was found to exhibit antifungal activity against all of the fungal isolates that were examined. The extract was particularly efficient against F. solani, F. oxysporium and M. phaseolina fungal isolates after 6 days of incubation, but less effective against A. Niger fungal isolates⁴⁷. In another study by Rai et al., 2015, antifungal activity of aqueous extract C. reflexa leaves was studies against two fungal species namely Candida albicans and Aspergillus fumigates at different concentrations. The results revealed that the extract showed concentration dependant inhibition of fungal growth against both the fungal species with more potent effect towards Candida albicans⁴⁸. A new phytoconstituent namely 3’,4’-dimethoxy-1-phenyl-1a, 2-ethanediol from the C. reflexa Roxb. stem showed potent antifungal activity againstthree fungal species Candida albicans and Candida kefyr^32,49.

Antiviral activity:

In an investigation by Mahmood et al., 1997, crude aqueous extract of C. reflexa was found to exhibit potent anti-HIV activity. This activity was attributed towards the phytoconstituents such as flavones, flavones and quinic acid derivatives and combinational effects of nine closely similar compounds isolated from C. reflexa⁵⁰. From the aqueous extract of C. reflexa, an antiviral protein with a substantial inhibitory activity was identified⁵¹.

Immunomodulatory activity:

Ayurveda emphasizes herbal medicines and therapies. The Ayurvedic medical system is one of the oldest, and it entails a wide range of ethnopharmacological practices. It contains various herbs that have been shown to improve physical and mental health, strengthen the body's defense mechanisms, immune system and lengthen life⁵². There are several herbal medications documented for their immunomodulatory effects⁵³. They may have a generic effect on the host's ability to resist infections and malignancies, or they may have a specific effect on the host's ability to react to foreign material. Immunomodulators affect the immune system's intricate web of systems in unknown ways, allowing the body to fight sickness and protect organs and tissues from harm⁵⁴. The immune system is not restricted to a single part of the body. Immune stem cells can either stay in the bone marrow until they mature or they can move to other places of the body to mature. As a result, the majority of immune cells travel throughout the body, exerting distinct impacts. The system has two unique but overlapping ways of fighting incursive organisms: antibody-mediated immunity and cell-mediated immunity⁵⁵.C. reflexa is one of such plant documented for its immunomodulatory activity. An ayurvedic Kwath formulation of C. reflexa was investigated for free radical scavenging activity in RAW 264.7 cell line and splenocyte proliferation assay for Th1/Th2 immunomodulatory potential by flow cytometer. The results revealed that the Kwath formulation of C. reflexa showed potent antioxidant and immunomodulatory activity and thus suggested its usefulness as value-added nutraceuticals⁵⁶.

Traditional applications:

C. reflexa has a wide range of traditional uses. Its juice is used as an inhalation treatment for jaundice and shows antiemetic activity²¹. The poultice of C. reflexais used in the treatment of rheumatism, gout, and headache. Its stem is used for biliary disorders, flatulence, constipation and other liver ailments, while the fruits are used to treat cough and fever. The seeds of C. reflexa are used in diseases of the liver and spleen also used as hair growth stimulants and the whole plant of C. reflexa is useful for curing gallbladder disorders and mental illnesses¹⁴.

CONCLUSION:

C. reflexa is a rich and diverse source of a wide range of useful compounds. Flavonoids, alkaloids, lignans, polysaccharides, steroids, volatile oils, and resinous glycosides are abundant in this plant. Prehistoric manuscripts mention the therapeutic value of its various kinds. It is traditionally thought to be a miraculous genus with a wide range of medicinal properties. Traditional medicinal systems use herbal prescriptions such as decoctions, extracts, pastes, powders, juices, and infusions made from various parts of the plant. According to the findings of this study. It has been well documented for its anti-infective, anti-inflammatory, immunomodulatory and anticancer activity of C. reflexa is unpopular among the general public but is well-known among traditional and indigenous peoples in various Indian states. It's been employed in medical and ethnoveterinary settings. The plant's research endeavours have virtually little impact in India and overseas. To establish a healthier India with this amazing ethnomedicinal plant, advanced scientific research is urgently needed.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

Authors are grateful to the Dean School of Health Sciences and Technology, Dr. Vishwanath Karad MIT World Peace University for providing us with the opportunity to write this article.

REFERENCES:

1. Pujari R. Thakurdesai P. Fenugreek in management of immunological, infectious, and malignant disorders. In Fenugreek: Traditional and Modern Medicinal Uses. 2022; 1: 474.

2. Vyawahare N. Pujari R. Kagathara V. Gangurde P. Bodhankar S. Hadambar A. Central nervous system activity of Argyriea Speciosa. Journal of Pharmaceutical Research. 2009; 8(3): 152-8.10.18579/jpcrkc/2009/8/3/79742

3. Suresh V. Sruthi V. Padmaja B. Asha VV. In vitro anti-inflammatory and anti-cancer activities of Cuscuta reflexa Roxb. J Ethnopharmacol. 2011; 134(3): 872-7. https://doi.org/10.1016/j.jep.2011.01.043

4. Gawade A. Boldhane S. Pawar A. Pujari R. Kuchekar A. In vivo evaluation for the anticoagulant activity of dipyridamole matrix tablets. Research Journal of Pharmacy and Technology. 2023; 16(7): 3104-8. 10.52711/0974-360X.2023.00510

5. Ashraf R. Shaheen H. Firdous S. S. Mehmood A. Habib T. Hussain MA. Comparative in vitro biological activity analysis of Cuscuta reflexa Roxb. and C. campestris Yuncker. Bangladesh Journal of Botany. 2020; 49(2): 249-56. 10.3329/bjb.v49i2.49298

6. Nooreen Z. Tandon S. Yadav NP. Ahmad A. New chemical constituent from the stem of Cuscuta reflexa Roxb. and its biological activities. Nat Prod Res. 2021; 35(14): 2429-32. https://doi.org/10.1080/14786419.2019.1669033

7. Udavant PB. Satyanarayana SV. Upasani CD. Preliminary screening of Cuscuta reflexa stems for anti inflammatory and cytotoxic activity. Asian Pacific Journal of Tropical Biomedicine. 2012; 2(3): S1303-7. https://doi.org/10.1016/S2221-1691(12)60405-5

8. Kandekar U.Pujari R. Nanocarriers for breast cancer: Advanced perspective. Hacettepe University Journal of the Faculty of Pharmacy. 2021; 41(3): 177-93. https://doi.org/10.52794/hujpharm.891355

9. Pujari RR. Bandawane DD. 2-Pyrocatechuic acid attenuates carboplatin induced hematological toxicities in Wistar rats. Research Journalof Pharmacy and Technology. 2022; 15(3): 1053-8.10.52711/0974-360X.2022.00176

10. Khan AA. Bashir F. Akhtar J. Anjum N. Alam S. Phyto-chemical and pharmacological investigations of Aftimoon (Cuscuta reflexa). International Journal of Unani and Integrative Medicine. 2019; 3(3): 45-8. 10.33545/2616454X.2019.v3.i3a.95

11. Khan A. Siddiqui A. Jamal A. Traditional uses, chemistry and pharmacological activities of Cuscuta reflexa Roxb: A compendious review. International Journal of Scientific Research and Review. 2018; 7(10): 685-93.

12. Saini P. Mithal R. Menghani E. A parasitic medicinal plant Cuscuta reflexa: an overview. Int J Sci Eng Res. 2015; 6 (12): 951-9.

13. Biswal B. Panda SK. GC-MS Analysis of the methanolic extract of Cuscuta reflexa Roxb. and Gymnema sylvestre (Retz.) R. Br. ex. Sm. Research Journal of Pharmacy and Technology. 2023; 16(1): 18-22. 10.52711/0974-360X.2023.00004

14. Lalchand SR. Rakshpal G. Prakash RO. Cuscuta reflexa (Dodder plant): A critical review on the medicinal plant used in ayurveda. International Journal of Research in Ayurveda and Pharmacy. 2017; 8(6): 38-42.10.7897/2277-4343.086288

15. Riaz M. Bilal A. Ali MS. Fatima I. Faisal A. Sherkheli MA.AsgharA.Natural products from Cuscuta reflexa Roxb. with antiproliferation activities in HCT116 colorectal cell lines. Natural Product Research. 2017; 31(5): 583-7. 10.1080/14786419.2016.1198349

16. Katiyar NS. Singh AP. Gangwar AK. Rao NV. Evaluation of carrageenan induced antiinflammatory activity of stem extracts of Cuscuta reflexa (Roxb) in rats. Int J Res Pharm Chem. 2015; 5: 322-6. http://ijrpc.com/files/21-04-15/11-576.pdf

17. Kalita D. Saikia J. Ethonomedicinal, antibacterial and antifungal potentiality of Centella asiatica, Nerium indicum and Cuscuta reflexa-widely used in Tiwa tribe of Morigaon district of Assam, India. International Journal of Phytomedicine. 2012; 4(3): 380-5.

18. Perveen S. Bukhari IH. Kousar S. Rehman J. Antimicrobial, antioxidant and minerals evaluation of Cuscuta europea and Cuscuta reflexa collected from different hosts and exploring their role as functional attribute. International Research Journal of Pharmaceutical and Applied Sciences. 2013; 3(5): 43-49. http://www.irjpas.com/view_content.php?quat=3&date=Volume-3:Issue-5 (Sep-Oct, 2013)&issue=5

19. Firdous AM. Sofi MA. Evaluation of antihistaminic activity of herbal drug isolated from Cuscuta reflexa Roxb. Annals of Plant Sciences. 2017; 6(11): 1897-910.10.21746/aps.2017.6.11.15

20. Tanruean K. Kaewnarin K. Suwannarach N. Lumyong S. Comparative evaluation of phytochemicals and antidiabetic and antioxidant activities of Cuscuta reflexa grown on different hosts in northern Thailand. Natural Product Communications. 2017; 12(1): 51-4. PMID: 30549823

21. Muhammad N. Ullah S. Abu-Izneid T. RaufA. Shehzad O. Atif M. Khan H. Naz H. Herrera-Calderon O. Khalil AA. The pharmacological basis of Cuscuta reflexa whole plant as an antiemetic agent in pigeons. Toxicology Reports. 2020; 7: 1305-10.10.1016/j.toxrep.2020.09.009

22. Borole S. Oswal R. Antre R. Kshirsagar S. Bagul Y. Evaluation of anti-epileptic activity of Cuscuta reflexa Roxb. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2011; 2(1): 657-63.

23. Awasthi L. The purification and nature of an antiviral protein fromCuscuta reflexa plants. Archives of Virology. 1981; 70(3): 215-23. https://doi.org/10.1007/bf01315128

24. Bhattacharya S. Roy B. Preliminary investigation on antipyretic activity of Cuscuta reflexa in rats. Journal of Advanced Pharmaceutical Technology and Research. 2010; 1(1): 83. PMID:22247835

25. Gupta M. Mazumder U. Pal D. Bhattacharya S. Anti-steroidogenic activity of methanolic extract of Cuscuta reflexa roxb. stem and Corchorus olitorius Linn. seed in mouse ovary. 2003; 41(6): 641-4. PMID:15266914

26. Dokuparthi SK. Banerjee N. Kumar A. Singamaneni V. Giri AK. Mukhopadhyay S. Phytochemical investigation and evaluation of antimutagenic activity of the extract of Cuscuta reflexa Roxb by Ames Test. International Journal of Pharmaceutical Sciences and Research. 2014; 5(8): 3430. http://dx.doi.org/10.13040/IJPSR.0975-8232.5(8).3430-34

27. Soni N. Dhiman RC. Larvicidal activity of Zinc oxide and titanium dioxide nanoparticles Synthesis using Cuscuta reflexa extract against malaria vector (Anopheles stephensi). Egyptian Journal of Basic and Applied Sciences. 2020; 7(1): 342-52.10.1080/2314808X.2020.1830236

28. Tambe V. Pujari R. Karnik A. Dongre P. Pterostilbene: A review on its pharmacological activities. Research Journal of Pharmacy and Technology. 2023; 16(11): 5514-21. 10.52711/0974-360X.2023.00892

29. Sawant R. Baghkar A. Jagtap S. Harad L. Chavan A. Khan N A. Yeval RP. Kale MK. A review on - Herbs in Anticancer. Asian Journal of Research in Pharmaceutical Sciences. 2018; 8 (4): 179-184.10.5958/2231-5659.2018.00031.0

30. Bhagat M. Arora JS. Saxena AK. In vitro and in vivo antiproliferative potential of Cuscuta reflexa Roxb. Journal of Pharmacy Research. 2013; 6(7): 690-5.10.1016/j.jopr.2013.06.005

31. Mishra S. Rawal JA. Sahu RK. Evaluation of chemoprotective and anticarcinogenic activity of Cuscuta reflexa. Pharmaceutical and Biosciences Journal. 2019; 33-39.

32. Noureen S. Noreen S. Ghumman SA. Batool F. Bukhari SNA. The genus Cuscuta (Convolvolaceac): An updated review on indigenous uses, phytochemistry, and pharmacology. Iran J Basic Med Sci. 2019; 22(11): 1225-52.

33. Pujari RR. Bandawane DD. Comparative studies on protective efficacy of gentisic acid and 2-pyrocatechuic acid against 5-fluorouracil induced nephrotoxicity in Wistar Rats. 2022; 60(4): 241-7.

34. Mishra S. Alhodieb FS. Barkat MA. Hassan MZ. Barkat HA. Ali R. Alam P. Alam O. Antitumor and hepatoprotective effect of Cuscuta reflexa Roxb. in a murine model of colon cancer. J Ethnopharmacol. 2022; 282: 114597.10.1016/j.jep.2021.114597

35. Pujari RR. Bandawane DD. Hepatoprotective activity of gentisic acid on 5-fluorouracil-induced hepatotoxicity in wistar rats. Turk J Pharm Sci. 2021; 18(3): 332-8.10.4274/tjps.galenos.2020.95870

36. Chatterjee D. Sahu DR. Jha A. Dwivedi J. Evaluation of antitumor activity of Cuscuta reflexa Roxb (Cuscutaceae) against Ehrlich Ascites Carcinoma in Swiss albino mice. Tropical Journal of Pharmaceutical Research. 2011; 10. https://doi.org/10.4314/tjpr.v10i4.10

37. Hassan W. Buabeid MA. Kalsoom U. Bakht S. Akhtar I. Iqbal F. Arafa EA. Cuscuta reflexa Roxb. expedites the healing process in contact frostbite. Biomed Res. Int. 2020; 2020: 4327651. https://doi.org/10.1155/2020/4327651

38. Upadhye M. Salvi V. Pujari R. Chanshetti R. Joshi U. Analgesic activity of roots of Holostemma annulare. Research Journal of Pharmacology and Pharmacodynamics. 2011; 3(2): 77-80. https://rjppd.org/AbstractView.aspx?PID=2011-3-2-17

39. Udavant P. Suggala VS. Kshirsagar SJ. Upasani CD. Evaluation of analgesic and anti inflammatory activity of Cuscuta reflexa extracts on animal models. Indian Drugs. 2016; 53: 54-62.10.53879/id.53.10.10647

40. Pal DK. Mandal M. Senthilkumar GP. Padhiari A. Antibacterial activity of Cuscuta reflexa stem and Corchorus olitorius seed. Fitoterapia. 2006; 77(7-8): 589-91. https://doi.org/10.1016/j.fitote.2006.06.015

41. Sonmez PE. Kirbağ S.Şule I. Antifungal and antibacterial effect of dodder (Cuscuta campestris) used for hepatitis treatment of mothers and newborn infants in province Mardin in Turkey. Yuzuncu Yıl Universitesi Tarım Bilimleri Dergisi. 2019; 29(4): 722-30. https://doi.org/10.29133/yyutbd.605970

42. Gulati D. Mishra A. Evaluation of antibacterial activity of Cuscuta reflexa Roxb. International Journal of Pharmacy. 2016; 6(4): 83-6.

43. Manore D. Pillai S. Joshi A. Punashiya R., Preliminary phytochemical screening and antibacterial activity of ethyl acetate extract of Cuscuta reflexa Roxb. Research Journal of Pharmacy and Technology. 2012; 5(1): 79-82.

44. Mishra S. Dixit N. Investigations on anti-bacterial effect of extract Cuscuta reflexa. Asian Journal of Pharmacy and Pharmacology. 2019; 5(2): 419-24.

45. Neetu B. Comparative study of antibacterial activity of ethyl acetate extract of Cuscuta reflexa Grown on Cassia fistula and Ficus benghalensis. International Journal of Pharmaceutical Sciences and Research. 2014; 5: 137-41. http://dx.doi.org/10.13040/IJPSR.0975-8232.5(1).137-141

46. Jagtap MD. Asabe AS. Telave AB. Mali BS.Chavan SJ. Kanade MB. Antifungal potential of Cuscuta reflexa Roxb. Central European Journal of Experimental Biology. 2014; 3(3): 30-32.

47. Mukhtar I.Atiq MN. Hanan A. Iqbal Z. Antifungal activity of Cuscuta reflexa Roxb. Pakistan Journal of Phytopathology. 2012; 24: 163-6.

48. Rai DK. PalA. Comprative evaluation of antifungal activity of Cuscuta reflexa (morning glory) Convolvulaceae. World Journal of Pharmaceutical Research. 2015; 4(11): 1341-7. http://www.wjpr.net/dashboard/abstract_id/4091

49. Nooreen Z. Tandon S. Yadav NP.Ahmad A. New chemical constituent from the stem of Cuscuta reflexa Roxb. and its biological activities. Natural Product Research. 2021; 35(14): 2429-32. https://doi.org/10.1080/14786419.2019.1669033

50. Mahmood N. Piacente S. Burke A. Khan A. Pizza C. Constituents of Cuscutareflexa are anti-HIV agents. Antiviral Chemistry and Chemotherapy. 1997; 8(1): 70-4. https://doi.org/10.1177/095632029700800108

51. Jagtap A. Vyawahare N. Shinde N. Kakade S. Pujari R. Immunomodulatory activity of ethanolic extract of Dodonaea viscosa LF. Pharmacologyonline. 2011; 2: 685-701.

52. Sasmal A. Urolagin D. Immunomodulatory activity of Cestrum nocturnum - A comprehensive review. Asian Journal of Pharmacy and Technology. 2022; 12(1): 33-7. 10.52711/2231-5713.2022.00006

53. Manna R. VermaP. A review on Saraca indica – for immunomodulatory activity. Asian Journal of Pharmacy and Technology. 2023; 13(2): 135-8. 10.52711/2231-5713.2023.00025

54. Taylor GS. Blackbourn DJ. Infectious agents in human cancers: lessons in immunity and immunomodulation from gamma herpes viruses EBV and KSHV. Cancer Letters. 2011; 305(2): 263-78.10.1016/j.canlet.2010.08.019

55. Kumar D. Arya V. Kaur R. Bhat ZA. Gupta VK. Kumar V. A review of immunomodulators in the Indian traditional health care system. Journal of Microbiology, Immunology and Infection. 2012; 45(3): 165-84. https://doi.org/https://doi.org/10.1016/j.jmii.2011.09.030

56. Singh A. Singh V. Anantha RK. Evaluation of immunomodulatory and antioxidants properties of Kwath, conventional extracts in plants Cocculus hirsutus and Cuscuta reflexa - in vitro&ex vivo studies. J Ayurveda Integr Med. 2022; 13(1): 100537.10.1016/j.jaim.2021.100537

Received on 28.12.2023 Modified on 21.05.2024

Research J. Pharm. and Tech 2024; 17(10):5055-5061.

DOI: 10.52711/0974-360X.2024.00777

Sr. No.	Extract	Chemical Constituents	Organisms	Concentrations and results
1.	50% ethanolic, 100% chloroform	Strospeside, gitoxigenin, ursolic acid, odoroside-H, neritaloside, strospeside, gitoxigenin, ursolic acid, ursolic 4-O-p-coumaroyl-Oglycoside, methyl cinnamate, B-sitosterol glucoside, dihydroajugapitin	Pseudomonas aeruginosa, Bacillus substilis Shigella flexineri, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermis	Chloroform extract of C. reflexa was found to be more efficient against various bacteria than the 50% ethanolic extract⁴⁴.
2	Methanolic extract	Cuscutin, amarbelin, myricetin, quercitin, coumarin and oleanolic acid	Gram-positive bacteria like Bacillus subtilis, Staphylococcus aureus and gram-negative bacteria like Escherichia coli, Pseudomonas aeruginosa	50µg/ml, 100µg/ml, 150µg/ml, 200µg/ml, showed more activity against gram-negative bacteria as compared to gram-positive bacteria⁴².
3	Ethyl acetate extract	Cardiac glycosides, phenols and tannins	Salmonella typhi, Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae, Staphylococcus aureus	50, 100, 150 and 200mg/ml, C. reflexa cultured on Cassia fistula exhibited significantly improved activity against all pathogenic bacteria with inhibition zones ranging from 14.18-22.5mm at 100mg/ml concentration but extract was inert against Salmonella typhi at all concentrations tested⁴⁵