Available online on 15.02.2024 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright   © 2024 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                                               Review Article

Exploring the Therapeutic Potential: Phytochemistry and Pharmacology of Bryophyllum pinnatum

Saurabh Dhumane¹, Tejas Naik²*, Mahesh Shelke², Kiran Dukare², Krushna Dhongade²

¹ Assistant Professor, Department of Pharmaceutical Analysis, Samarth College of Pharmacy, Belhe, Pune, Maharashtra, India

² Department of Pharmacy, Samarth College of Pharmacy, Belhe, Pune, Maharashtra, India

Introduction: 

Bryophyllum pinnatum is a succulent plant in the Crassulaceae family that goes by several names, including the air plant, cathedral bells, life plant, and miracle leaf. This perennial herb, which originated in Madagascar, has spread to many tropical and subtropical areas of the world. There, it is frequently grown for both decorative and therapeutic purposes.  Bryophyllum pinnatum is characterized by fleshy, succulent leaves that are arranged in an alternate pattern along its stems.¹ The leaves are green and often have a serrated or lobed margin. One distinctive feature of the plant is the presence of small plantlets that develop along the margins of the leaves, which can fall to the ground and take root, giving rise to new plants. The plant has a sturdy stem and can grow up to 1 to 2 meters in height. While native to Madagascar, Bryophyllum pinnatum has become naturalized in various tropical and subtropical regions, including parts of Asia, Australia, and the Americas. It is well adapted to a variety of habitats, including rocky terrain, open woodlands, and disturbed areas.² The plant's ability to reproduce through both seeds and vegetative propagation contributes to its widespread distribution. Bryophyllum pinnatum has cultural significance in traditional medicine practices in some regions. Various parts of the plant, including leaves and stems, are believed to possess medicinal properties. In traditional medicine, it has been used to treat that while the plant has been traditionally used in folk medicine, scientific evidence supporting its medicinal efficacy is limited, and caution should be exercised. Bryophyllum pinnatum, commonly known as the "miracle leaf" or "life plant," has been the subject of interest in traditional medicine for its potential medicinal properties, including its purported activity in addressing kidney stones.³ Kidney stones, or renal calculi, are solid deposits that form in the kidneys from minerals and salts in the urine. These stones can cause severe pain and discomfort when they obstruct the urinary tract.⁴ While conventional medical treatments exist, some traditional practices involve the use of Bryophyllum pinnatum as a natural remedy for kidney stones.⁵

Morphology:

Bryophyllum pinnatum is a succulent herb, standing at a height of 0.3-1.2 meters. The stems are obtusely four-angled, with older ones displaying a pale coloration while younger ones exhibit a reddish hue with white undertones.¹⁰The leaves, typically simple or compound, feature an upper arrangement of 3-5/7 foliolate leaves with long petioles.¹¹

At the terminal ends of the stems, the bell-shaped, drooping flowers, which may reach a length of 7 centimeters, cluster into branching clusters to create terminal inflorescences. Every bloom is carried by a 10–25 mm stalk, or pedicel, which is attached to the tubular calyx partly.¹² There are patches of pink or reddish-colored hue across the calyx. The 3-6 centimeter-long petals, which range in color from yellowish-green to dark red, are also partially united into a tube called a corolla tube. The corolla tube splits into four petal lobes close to the apex. Winter and spring are the seasons when flowers blossom most commonly.¹³

Table 1: Classification and Morphological characteristics of Bryophyllum pinnatum

Chemical constituent 

Bryophyllum pinnatum, rich in diverse chemical constituents, showcases a complex profile with a range of bioactive compounds.⁶ The plant is identified for having a variety of macro and microelements as well as alkaloids, flavonoids, tannins, phenolic compounds, and saponin glycosides. Among the macro elements are magnesium, calcium, potassium, sodium, and phosphorous, while microelements include iron and zinc.⁷ Additionally, the plant is a source of essential vitamins, encompassing ascorbic acid, riboflavin, thiamin, and niacin .Further chemical analysis reveals the presence of specific acids, including syringic acid, caffeic acid, 4-hydroxy-3-methoxy cinnamic acid, 4-hydroxy benzoic acid, parahydroxy cinnamic acid, para coumaric acid, ferulic acid, protocatechuic acid, and phosphoenolpyruvate.⁸ The leaves of Bryophyllum pinnatum are particularly rich in compounds such as protocatechuic acid, astragalin, luteolin, rutin, kaempferol, quercetin, and kaempferol-o-glycosides. Among its ingredients, three flavonoids differentiate out as they have been discovered and separated, proving their important function in providing antileishmanial action. The plant also includes Bryophyllin A, B, C, and Bryophyllon, which are examples of bufadienolides.⁹

Many different chemical components have been identified in Bryophyllum pinnatum, and these elements have been linked to the plant's medicinal properties.

Alkaloids: The plant's alkaloids have a variety of pharmacological actions. Certain alkaloids have the ability to diuretic, which can help in the excretion of certain kidney stones. However, Bryophyllum pinnatum's particular alkaloids and their effect on kidney stones.¹⁴ 

Flavonoids: Flavonoids are substances found in Bryophyllum pinnatum that have been identified for their ability to act as antioxidants. The ability of flavonoids to lower oxidative stress—which may contribute to the development of kidney stones—has been investigated.¹⁵

Triterpenoids: These are another class of plant-found chemicals. Triterpenoids have been investigated for their diuretic and anti-inflammatory properties, which may have an impact on kidney stone treatment.¹⁶

Betalains: Some varieties of Bryophyllum pinnatum contain betalains, which are pigments with potential antioxidant properties.¹⁷

Bufadienolides: Thirteen bufadienolides have been reported in Bryophyllum pinnatum, and among them, three are glycosides.¹⁸ Glycosides are compounds that contain a sugar molecule. These bufadienolides exhibit various bioactivities, notably cytotoxic and insecticidal properties. Cytotoxicity refers to the ability to kill or inhibit the growth of certain cells, while insecticidal properties suggest toxicity to insects.¹⁹ Several bufadienolides, including Bersaldegenin-1-acetate, Bersaldegenin-1,3, 5-orthoacetate, Bryotoxin C, and glycosides Bryophyllins A, have been found in all species of Kalanchoe pinnata.²⁰ This indicates a widespread distribution of these compounds in this plant species. Bryophyllum C and B have been reported only in Kalanchoe pinnata, suggesting that these bufadienolides are specific to this particular species.²¹ Methyl daigremonate has been identified only in Bryophyllum daigremontianum, emphasizing that certain bufadienolides are unique to specific Kalanchoe species.²¹

Flavonoids, phenols and phenylpropanoids: 

In Kalanchoe pinnata, a variety of flavonoids have been identified, showcasing a rich chemical composition that includes derivatives of kaempferol and quercetin, as well as flavone glycosides such as acacetin, diosmetin glycosides, and luteolin.²² Additionally, unique compounds like epigallocatechin-3-osyringate and ethenylamino-substituted anthocyanidin, with a biogenetically distinct structure, have been reported. The flavonoids identified in Kalanchoe pinnata encompass numerous derivatives, primarily kaempferol glycosides and quercetin.²³ The presence of flavone glycosides, including acacetin, diosmetin glycosides, and luteolin, adds to the diversity of flavonoids in the plant. Notably, epigallocatechin-3-osyringate and ethenylamino-substituted anthocyanidin, with their distinct biogenetic structures, contribute to the unique chemical profile of Kalanchoe pinnata.²⁴Aerial parts of the plant contain various other compounds, including ferulic acid, protocatechuric acid, phosphoenolpyruvate, protocatechuic acid, syringic acid, 4-hydroxy-3-methoxy-cinnamic acid, 4-oh-benzoic acid, p-oh-cinnamic acid, and paracoumaric.²⁵The restricted occurrence of these flavonoids in Kalanchoe pinnata, coupled with their abundance in comparison to other species, suggests that flavonoids could serve as chemical markers for the plant.²⁶ This chemical richness may contribute to the therapeutic potential of Kalanchoe pinnata. Leaves of Kalanchoe pinnata have been found to contain astragalin, luteolin, kaempferol, and rutin, further highlighting the diversity of flavonoids in different plant parts.²⁷

Activity on Kidney Stones: Certain traditional use of Bryophyllum pinnatum indicate a diuretic effect. The minerals and other components that contribute to kidney stone development may be cleared out with increased urine output.²⁸ Since inflammation can be a significant role in kidney stones, the plant's anti-inflammatory qualities may help reduce kidney stones. The plant's antioxidants can help in lowering oxidative stress, which has been linked to the development of kidney stones.²⁹ According to some research, Bryophyllum pinnatum may have the ability to relax smooth muscle, which may help kidney stones flow through the ureter.³⁰

Habitat: Kalanchoe pinnata is naturally found in hot and humid tropical regions around the world. Specifically, it is native to Madagascar, an island nation off the southeastern coast of Africa. The plant thrives in warm climates and is often cultivated or found growing in various tropical and subtropical areas.³¹

Parts Used: In traditional medicine systems, almost all parts of the Kalanchoe pinnata herb have been utilized for the treatment of various ailments in folkloric practices. However, extensive research has primarily focused on the leaves of the plant.³²

The Ayurvedic properties:

Rasa: Kashaya (Astringent), Amla (Sour)

Guna: Laghu (Light)

Virya: Sheeta (Cool)

Vipaka: Madhura (Sweet)

Doshaghnata: Vatakaphahara (Balancing Vata and Kapha Doshas)

Karma (Actions): Ashmarighna (Stone-breaking, often referring to its potential in treating kidney stones), Vranaropaka (Wound healing), Mootrala (Diuretic), Shonita sthapana (Hemostatic, stopping bleeding), Rakta stambaka (Stopping bleeding), Grahi (Astringent, useful in diarrhea and promoting absorption)

Rogaghnata (Effectiveness in Diseases): Ashmari (Kidney stones), Atisara (Diarrhea), Raktasrava (Bleeding disorders), Visuchika (A type of intestinal disorder, often associated with dysentery)

These Ayurvedic properties suggest that Kalanchoe pinnata has a cooling nature (Sheeta Virya) and astringent taste (Kashaya Rasa), making it potentially beneficial in conditions associated with excess heat and bleeding.³³ The herb is also noted for its wound-healing and diuretic properties. The balance of Vata and Kapha doshas indicates its potential to address disorders related to these energies in the body.³⁴

Figure 1: Bryophyllum pinnatum

Pharmacological activities of Bryophyllum pinnatum

Diuretic and anti-urolithiatic activity: 

According to recent studies, the diuretic and anti-urolithiatic activities of Kalanchoe pinnata were investigated.³⁵ In these studies, a hydroalcoholic extract of the leaves was administered to male Wistar rats, both orally and intraperitoneally. The assessment of diuretic and anti-urolithiatic effects involved observing the urine output, measured by comparing the urine volume collected from individual animals placed in metabolic cages.³⁶ The findings of the study indicated that the extract exhibited significant diuretic and anti-urolithiatic activities.³⁷ Notably, when the extract was administered intraperitoneally, it demonstrated a more potent diuretic effect compared to oral administration. This suggests that the mode of administration plays a role in the intensity of the diuretic response.³⁸ These results contribute to the understanding of the therapeutic potential of Kalanchoe pinnata in the management of conditions related to diuresis and urolithiasis.³⁹

Anti-depressant activity:  

Kalanchoe pinnata has been studied in animal models to assess its effects on the central nervous system. ³² The observed sedative and CNS depressant actions suggest an influence on the neurological and behavioral aspects of the animals. ⁴⁰ The leaf extract of Kalanchoe pinnata has been found to have the ability to increase the levels of the neurotransmitter GABA in the brain.⁴¹

Anti-fungal activity: 

The research aimed to explore the antifungal properties of traditional Nigerian herbs, with a specific emphasis on their efficacy against strains of Candida species responsible for vaginal candidiasis.⁴² Various strains of Candida species, including Candida albicans, C. glabrata, C. tropicalis, and C. pseudotropicalis, were used in the evaluation of the antifungal activity of Kalanchoe pinnata.⁴³ The ethanolic extract of Kalanchoe pinnata was used in the study to assess its inhibitory effects on the different Candida species.⁴⁴  The findings revealed that none of the strains of C. pseudotropicalis were inhibited by the ethanolic extract of Kalanchoe pinnata.¹⁰ In contrast to the limited inhibitory effects on C. pseudotropicalis, the ethanolic extract demonstrated positive antifungal effects on other species of Candida, such as C. albicans, C. glabrata, and C. tropicalis.⁴⁵

Hepatoprotective activity:

The hepatoprotective activity of Bryophyllum pinnatum was assessed through in vivo and in vitro histopathological studies in rats, administered orally.¹⁴ The comparison between the aqueous extract or juice of the leaves and the ethanol extract revealed that the aqueous extract demonstrated greater efficacy. In either in vivo and in vitro evaluations, the aqueous extract or juice exhibited superior hepatoprotective effects when compared to the ethanol extract of Bryophyllum pinnatum.⁴⁶ This suggests that the administration of the plant's aqueous extract was more effective in preserving liver health, as evidenced by histopathological examinations in rat models.⁴⁷Interestingly, while the ethanol extract of Bryophyllum pinnatum also demonstrated hepatoprotective activity, the findings highlight the relatively heightened effectiveness of the aqueous extract or juice.⁴⁸

Antileishmanial activity

Bryophyllum pinnatum's antileishmanial action has been demonstrated by the separation and identification of certain flavonoids, one of which is quercitrin.⁴⁹ The plant's methanolic extract effectively isolated this flavonoid, highlighting the critical role flavonoids play in the plant's ability to prevent leishmaniasis.⁵⁰  Among the flavonoids that have been found, quercitrin, quercetin, and ofzelin have been found to be significant contributions to the antileishmanial activity that Bryophyllum pinnatum exhibits. Their presence suggests a synergistic effect that might improve the plant's therapeutic benefit against the parasitic illness leishmaniasis, which is brought on by the Leishmania parasite.⁵¹ Quercitrin, in particular, stands out as a significant compound, showcasing its potential as a key component in the plant's antileishmanial properties.⁵² The isolation and recognition of these flavonoids not only contribute to our understanding of the plant's pharmacological activities but also the way for further exploration of these compounds in the development of novel antileishmanial treatments.⁵³

Anti-oxidant activity: 

The leaves of Kalanchoe pinnata demonstrate maximum scavenging effects, indicating a potent ability to neutralize free radicals. The ethanolic extract of Kalanchoe pinnata exhibits higher total phenolic and flavonoid content compared to other extracts.⁵⁴ The high antioxidant activity of Kalanchoe pinnata is attributed to the presence of a significant number of flavonoids and phenols in the extract. Phenolic constituents in the extract have the ability to interact with transition metals by filling their aqua coordination sites.⁵⁵ This interaction can result in the generation of metal coordinates and insoluble complexes, contributing to antioxidant effects. Phenolic compounds, such as flavonoids, are known for their chelation properties, forming stable complexes with metal ions.⁵⁶ This chelation can prevent the metals from participating in oxidative processes. Flavonoids are known for their strong antioxidant properties, and their presence in high amounts contributes to the overall antioxidant activity of the plant extract.⁵⁷ Phenolic compounds, including flavonoids, are effective at scavenging free radicals, preventing oxidative stress, and offering protection against various diseases.⁵⁸

Anti-pyretic activity

Test animals, specifically rats, were subjected to hyperthermic conditions. Pyrexia, or fever, was induced in the rats using brewer's yeast.⁵⁹ The laboratory specimens (rats) were administered a hydroalcoholic extract of Kalanchoe pinnata. The administration of the hydroalcoholic extract of Kalanchoe pinnata resulted in a reduction in body temperature in the hyperthermic rats. The observed reduction in body temperature indicated the antipyretic efficacy of Kalanchoe pinnata.²⁴ The antipyretic activity of Kalanchoe pinnata is attributed to the flavonoids content in the plant extract.⁶⁰ The ability of Kalanchoe pinnata to reduce fever in the experimental model suggests its potential application as an antipyretic agent.¹⁴ Flavonoids, which are known for their diverse biological activities, including anti-inflammatory properties, may contribute to the antipyretic effects observed in the study.⁶¹

Anti-tussive activity

Aqueous extract of Bryophyllum pinnatum demonstrated notable antitussive and antihistaminic effects in guinea pigs, particularly in the context of ovalbumin sensitivities. ⁶² Guinea pigs subjected to doses of 200 and 400 mg/kg/day of the aqueous extract over a 21-day period exhibited enhanced resistance to the effects of histamine exposure, achieved through an aerosol containing 0.2% histamine in a glass chamber.⁶³ In the treated group, the time elapsed before the onset of preconvulsive dyspnea substantially increased, indicating a significant antitussive effect. Notably, the administration of 400 mg/kg/day led to a pronounced reduction in phenol red secretion, while both dosage levels resulted in a reduction in coughing fits. Additionally, the aqueous extract exhibited the ability to decrease mucus viscosity in the sensitized group, comparable to the effects observed with the administration of salbutamol at 5 mg/kg/day.⁶⁴ Moreover, several physiological parameters underwent significant changes in response to the extract, including white blood cell counts, tracheal morphometry, and lymphocyte counts.⁶⁵ These findings collectively underscore the potential of Bryophyllum pinnatum's aqueous extract in mitigating histamine-induced respiratory distress, suggesting its utility as a promising natural remedy with antitussive and antihistaminic properties.⁶⁶

Medicinal application:

The juice extracted from the leaves of Bryophyllum pinnatum serves various medicinal purposes, including its use as a remedy for kidney stones.⁴⁹ The root extract is employed as a laxative and diuretic, beneficial for liver health, tuberculosis, and addressing mental disorders. The plant's healing properties extend to wound care, as evidenced by evaluations involving excision and incision.⁶⁷ Bryophyllum pinnatum has a versatile history of application, aiding in the treatment of diverse conditions such as body pain and skin issues.⁶⁸ Notably, it is recognized for its efficacy in facilitating the detachment of infants' umbilical cords.⁶⁹ The plant boasts anti-inflammatory, antimicrobial, antitumor, antiulcer, insecticidal, antidiabetic, and antioxidant properties. Boiling Bryophyllum pinnatum leaves yields a water extract used to treat fever, headache, and discomfort in the stomach.⁷⁰ This herb has proven to be quite beneficial, especially when it comes to treating stomach issues and kidney stones. Because of its many therapeutic benefits, it is a useful tool in conventional medicine.⁷¹

Conclusion: 

Bryophyllum pinnatum is renowned for its healing attributes, has been extensively utilized in traditional medicine to tackle diverse health concerns. This thorough investigation explores the plant's ethnomedicinal uses, phytoconstituents, and established pharmacological effects. The analysis not only examines its clinical applications but also takes into account toxicological considerations. The review emphasize the plant's extensive medicinal applicability across various regions globally, showcasing its effectiveness in addressing conditions like fever, ulcers, antimicrobial and antifungal activities, oxidative diseases diabetes, depression, insomnia, etc .

Despite existing clinical evidence supporting the plant's effectiveness in pregnancy management, the standardization and clinical assessment for numerous conditions, as indicated by experimental studies, remain pending. This underscores the necessity for additional research to meticulously evaluate the clinical efficacy of Bryophyllum pinnatum extracts and standardize products based on their active constituents. Bridging this gap will contribute to a more comprehensive comprehension of the plant's medicinal potential and facilitate its integration into clinical practice, benefiting individuals worldwide.

Acknowledgements: we would like to express our gratitude to all authors for their thoughtful contributions and collaborative spirit.

Conflict of Interest: All authors declare that no conflict of interest.

Funding: Not applicable

Ethics Statement: Not applicable

References:

1. Halberstein RA, Saunders AB. Traditional medical practices and medicinal plant usage on a Bahamian Island. Cult Med Psychiatry. 1978;2(2):177-203. https://doi.org/10.1007/BF00054583

2. Ahirwar K. Effective healthful medicinal plants as antilithiatic Agents. Journal of Pharmacognosy and Phytochemistry 2019; 8(3): 1849-1860

3. Choure K, Mukhija S, Gurnani C, Kumar V. Effect of PGRS on ornamental plant Bryophyllum pinnatum (LAM.) Kurz. Eur J Biomed Pharm Sci. 2016;3(1):348-53.

4. Monk R, Bushinski D. Kidney stones. In: Williams Textbook of Endocrinology. 2003;1411-25.

5. Pandhare RB, Shende RR, Avhad MS, Deshmukh VK, Mohite PB, Sangameswaran B, et al. Anti-urolithiatic activity of Bryophyllum pinnatum Lam. hydroalcoholic extract in sodium oxalate-induced urolithiasis in rats. J Tradit Complement Med. 2021;11(6):545-51. https://doi.org/10.1016/j.jtcme.2021.06.002 PMid:34765518 PMCid:PMC8572709

6. Souza L, Oliveira JP da S, Fernandes A da S, Macedo AF, Araujo-Lima CF, Felzenszwalb I. UHPLC-MS metabolomic profile and in silico pharmacokinetic approach of Kalanchoe daigremontiana Raym.-Hamet & H. Perrier aqueous extracts. J Pharm Biomed Anal. 2024;238. https://doi.org/10.1016/j.jpba.2023.115827 PMid:37951139

7. Sharma K, Chauhan ES. Comparative Study of Nutritional and Phytochemical Attributes of Andrographis paniculata, Bryophyllum pinnatum and Clitoria ternatea for Nutraceutical Applications. Curr Nutr Food Sci. 2018;15(6):600-7. https://doi.org/10.2174/1573401314666181024144113

8. Polya G. Biochemical Targets of Plant Bioactive Compounds : a Pharmacological Reference Guide to Sites of Action and Biological Effects. 2003;860. https://doi.org/10.1201/9780203013717 PMid:12901082

9. Ingole RD, Thalkari AB, Karwa PN, Zambare KK, Shinde PS. Bryophyllum pinnatum : A magical herb . Res J Pharmacogn Phytochem. 2020;12(3):162. https://doi.org/10.5958/0975-4385.2020.00027.8

10. Khurshid M. the Miracle Plant (Kalanchoe Pinnata): a Phytochemical and Pharmacological Review. 2015;(May 2011):2020.

11. Abd-El Maksoud H. Leaf Morphology of Some Species of Tribe Phaseoleae in Egypt. Egypt J Agric Sci. 2018;69(4):341-52. https://doi.org/10.21608/ejarc.2018.211698

12. Иванова ЛА, Вирачева ЛЛ. Семейство Crassulaceae J. St.-Hil. в коллекции оранжереи Полярно-альпийского ботанического сада. Проблемы Ботаники Южной Сибири И Монголии. 2019;1(18):584-8. https://doi.org/10.14258/pbssm.2019123

13. Embryology of Flowering Plants: Terminology and Concepts, Vol. 2. Embryol Flower Plants Terminol Concepts, Vol 2. 2005;

14. Fernandes JM, Cunha LM, Azevedo EP, Lourenço EMG, Fernandes-Pedrosa MF, Zucolotto SM. Kalanchoe laciniata and Bryophyllum pinnatum: an updated review about ethnopharmacology, phytochemistry, pharmacology and toxicology. Rev Bras Farmacogn. 2019;29(4):529-58. https://doi.org/10.1016/j.bjp.2019.01.012

15. Zeng X, Xi Y, Jiang W. Protective roles of flavonoids and flavonoid-rich plant extracts against urolithiasis: A review. Crit Rev Food Sci Nutr. 2019;59(13):2125-35. https://doi.org/10.1080/10408398.2018.1439880 PMid:29432040

16. Sethiya NK, Ahmed NM, Shekh RM, Kumar V, Kumar Singh P, Kumar V. Ethnomedicinal, phytochemical and pharmacological updates on Hygrophila auriculata (Schum.) Hiene: an overview. J Integr Med. 2018;16(5):299-311. https://doi.org/10.1016/j.joim.2018.07.002 PMid:30007830

17. Aguiar J, Gonçalves JL, Alves VL, Câmara JS. Chemical fingerprint of free polyphenols and antioxidant activity in dietary fruits and vegetables using a non-targeted approach based on quechers ultrasound-assisted extraction combined with UHPLC-PDA. Antioxidants. 2020;9(4). https://doi.org/10.3390/antiox9040305 PMid:32283793 PMCid:PMC7222190

18. Kamboj A, Saluja AK, Bryophyllum pinnatum (Lam.) Kurz.: Phytochemical and Pharmacological Profile: A Review. Pharmacognosy Reviews,2009,3,6,364-374

19. Zou D, Wang Q, Chen T, Sang D, Yang T, Wang Y, et al. Bufadienolides originated from toad source and their anti-inflammatory activity. Front Pharmacol. 2022;13. https://doi.org/10.3389/fphar.2022.1044027 PMid:36339575 PMCid:PMC9627299

20. Oufir M, Seiler C, Gerodetti M, Gerber J, Fürer K, Mennet-von Eiff M, et al. Quantification of Bufadienolides in Bryophyllum pinnatum Leaves and Manufactured Products by UHPLC-ESIMS/MS. Planta Med. 2015;81(12-13):1190-7. https://doi.org/10.1055/s-0035-1546126 PMid:26132852

21. Kolodziejczyk-Czepas J, Stochmal A. Bufadienolides of Kalanchoe species: an overview of chemical structure, biological activity and prospects for pharmacological use. Phytochem Rev. 2017;16(6):1155-71. https://doi.org/10.1007/s11101-017-9525-1 PMid:29200987 PMCid:PMC5696496

22. Veitch NC, Grayer RJ. Flavonoids and their glycosides, including anthocyanins. Nat Prod Rep. 2008;25(3):555-611. https://doi.org/10.1039/b718040n PMid:18497898

23. Nascimento LB dos S, Casanova LM, Costa SS. Bioactive Compounds from Kalanchoe Genus Potentially Useful for the Development of New Drugs. Life. 2023;13(3). https://doi.org/10.3390/life13030646 PMid:36983802 PMCid:PMC10058616

24. Fürer K, Simões-Wüst AP, Von Mandach U, Hamburger M, Potterat O. Bryophyllum pinnatum and Related Species Used in Anthroposophic Medicine: Constituents, Pharmacological Activities, and Clinical Efficacy. Planta Med. 2016;82(11-12):930-41. https://doi.org/10.1055/s-0042-106727 PMid:27220081

25. Kumar G, Kumar R, Rana H. The Pharmacological activities of mother of thousand (Kalanchoe pinnata). Res J Pharmacol Pharmacodyn. 2023;31-5. https://doi.org/10.52711/2321-5836.2023.00007

26. Muzitano MF, Tinoco LW, Guette C, Kaiser CR, Rossi-Bergmann B, Costa SS. The antileishmanial activity assessment of unusual flavonoids from Kalanchoe pinnata. Phytochemistry. 2006;67(18):2071-7. https://doi.org/10.1016/j.phytochem.2006.06.027 PMid:16930642

27. Yeshi K, Crayn D, Ritmejerytė E, Wangchuk P. Plant Secondary Metabolites Produced in Response to Abiotic Stresses Has Potential Application in Pharmaceutical Product Development. Molecules. 2022;27(1). https://doi.org/10.3390/molecules27010313 Mid:35011546 PMCid:PMC8746929

28. Vikas M, Anju D, Chhavi S, Singla C. An Update on Urolithiatic Plant Drugs as Alternative Treatment Option for Mitigation of Kidney Stones. Ann RSCB. 2020;24(2):507-37.

29. Nirumand MC, Hajialyani M, Rahimi R, Farzaei MH, Zingue S, Nabavi SM, et al. Dietary plants for the prevention and management of kidney stones: Preclinical and clinical evidence and molecular mechanisms. Int J Mol Sci. 2018;19(3). https://doi.org/10.3390/ijms19030765 PMid:29518971 PMCid:PMC5877626

30. Sonawani R, Singh K, Gupta PC. Kidney stone: A clinical review. IOSR J Pharm Biol Sci (IOSR-JPBS. 15(5):42-9.

31. Muzitano MF, Bergonzi MC, De Melo GO, Lage CLS, Bilia AR, Vincieri FF, et al. Influence of cultivation conditions, season of collection and extraction method on the content of antileishmanial flavonoids from Kalanchoe pinnata. J Ethnopharmacol. 2011;133(1):132-7. https://doi.org/10.1016/j.jep.2010.09.020 PMid:20883762

32. Akinpelu M, Gamade SM, Akinbo FSM, Adeniyi TD, TD Elizebeth TD, Obeagu EI, Histopathological and Biochemical Effect of Vitamin C and D on Phosphine-Induced Hepatotoxicity in Wistar Rats, Asian Journal of Dental and Health Sciences 2023;3(2):18-22 https://doi.org/10.22270/ajdhs.v3i2.40

33. Bhutya RK. Ayurvedic Medicinal Plants of India. Scientific Publishers, 2011;2:1-352.

34. Khalsa KPS, Tierra M. The Way of Ayurvedic Herbs: The Most Complete Guide to Natural Healing and Health with Traditional Ayurvedic Herbalism. 2008;29:189.

35. Sohgaura A, Bigoniya P, Nagar G, Pradesh M, Birendra Shrivastava I, Papiya Bigoniya C, et al. Diuretic potential of Cynodon dactylon, Emblica officinalis, Kalanchoe pinnata and Bambusa nutans. ~ 2895 ~ J Pharmacogn Phytochem. 2018;7(3):2895-900.

36. Patel S. Anti-Urolithiatic Activity Of Extracts of Plant - Mimosa Pudica L. In Rats. 2010;1-114.

37. Kumar A, Nandi MK, Kumar B, Kumar A, Kumar R, Singh AK, et al. Antiurolithiasis, Antioxidant, Anti-inflammatory, Analgesic, and Diuretic Activity of Ethanolic Extract of Seeds of Caesalpinia bonducella. Int J Pharm Investig. 2021;11(3):306-11. https://doi.org/10.5530/ijpi.2021.3.54

38. Maharana L, Dadhich OP. Review on role of herbal drug in the prevention and managment of kidney disease . An Int J Res AYUSH Allied Syst. 2016;3(1):500-8.

39. Dighade R, Ingole R, Ingle P, Gade A, Hajare S, Ingawale M. Nephroprotective effect of Bryophyllum pinnatum-mediated silver nanoparticles in ethylene glycol-induced urolithiasis in rat. IET Nanobiotechnology. 2021;15(3):266-76. https://doi.org/10.1049/nbt2.12011 PMid:34694671 PMCid:PMC8675820

40. Domino EF. Sites of Action of Some Central Nervous System Depressants. Annu Rev Pharmacol. 1962;2(1):215-50. https://doi.org/10.1146/annurev.pa.02.040162.001243

41. Pattewar S V. Kalanchoe Pinnata : Phytochemical and Pharmacological Profile. Int J Phytopharm. 2012;2(1). https://doi.org/10.7439/ijpp.v2i1.223

42. Hsu H, Sheth CC, Veses V. Herbal Extracts with Antifungal Activity against Candida albicans: A Systematic Review. Mini-Reviews Med Chem. 2020;21(1):90-117. https://doi.org/10.2174/1389557520666200628032116 PMid:32600229

43. Ogunshe AAO, Lawal OA, Iheakanwa CI. Effects of simulated preparations of plants used in Nigerian traditional medicine on Candida spp. associated with vaginal candidiasis. Ethnobot Res Appl. 2008;6:373-83. https://doi.org/10.17348/era.6.0.373-383

44. Stefanowicz-Hajduk J, Hering A, Gucwa M, Hałasa R, Soluch A, Kowalczyk M, et al. Biological activities of leaf extracts from selected Kalanchoe species and their relationship with bufadienolides content. Pharm Biol. 2020;58(1):732-40. https://doi.org/10.1080/13880209.2020.1795208 PMid:32715869 PMCid:PMC7470146

45. Bruschi ML, Dota KFD, Consolaro MEL, Svidzinski TIE. Antifungal activity of brazilian propolis microparticles against yeasts isolated from vulvovaginal candidiasis. Evidence-based Complement Altern Med. 2011;2011. https://doi.org/10.1093/ecam/neq029 PMid:21607012 PMCid:PMC3094883

46. Milad R, El-Ahmady S and Nasser Singab A. Genus Kalanchoe (Crassulaceae): A review of its ethnomedicinal, botanical, chemical and pharmacological properties. European J Med Plants. 2014;4(1):86-104. https://doi.org/10.9734/EJMP/2014/5901

47. Uboh F. Effect of Aqueous Extract of Psidium Guajava Leaves on Liver Enzymes, Histological Integrity and Hematological Indices in Rats. Gastroenterol Res. 2010; https://doi.org/10.4021/gr2010.02.174w PMid:27956982 PMCid:PMC5139837

48. Joshi B, Panda SK, Jouneghani RS, Liu M, Parajuli N, Leyssen P, et al. Antibacterial, Antifungal, Antiviral, and Anthelmintic Activities of Medicinal Plants of Nepal Selected Based on Ethnobotanical Evidence. Evidence-based Complement Altern Med. 2020;2020. https://doi.org/10.1155/2020/1043471 PMid:32382275 PMCid:PMC7193273

49. Kamboj A, Saluja AK. Bryophyllum pinnatum (Lam.) Kurz.: Phytochemical and pharmacological profile: A review. Pharmacogn Rev. 2009;3(6):364-74.

50. Ungogo MA, Ebiloma GU, Ichoron N, Igoli JO, de Koning HP, Balogun EO. A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora. Front Chem. 2020;8. https://doi.org/10.3389/fchem.2020.617448 PMid:33425860 PMCid:PMC7786139

51. Raj S, Sasidharan S, Balaji SN, Dubey VK, Saudagar P. Review on natural products as an alternative to contemporary anti-leishmanial therapeutics. J Proteins Proteomics. 2020;11(2):135-58. https://doi.org/10.1007/s42485-020-00035-w

52. Silva-Silva JV, Moragas-Tellis CJ, Chagas M do S dos S, Souza PVR de, Souza C da SF de, Hardoim D de J, et al. Antileishmanial Activity of Flavones-Rich Fraction From Arrabidaea chica Verlot (Bignoniaceae). Front Pharmacol. 2021;12. https://doi.org/10.3389/fphar.2021.703985 PMid:34354593 PMCid:PMC8329660

53. Nardella F, Gallé J-B, Bourjot M, Weniger B, Vonthron-Sénécheau C. Antileishmanial and Antitrypanosomal Activities of Flavonoids. 2018;163-94. https://doi.org/10.1007/978-3-319-67045-4_7

54. Ophelia George L, Radha HR, Somasekariah B V. In vitro anti-diabetic activity and GC-MS analysis of bioactive compounds present in the methanol extract of Kalanchoe pinnata. Indian J Chem. 2018;57:1213-21.

55. Dhakar RC, Prajapati SK, Maurya SD, Tilak VK, Das MK, Das S, Verma KK, Jain N. Antioxidant Potential of Cordia dichotoma: A Review. Asian Journal of Dental and Health Sciences, 2021;1(1):19-23. https://doi.org/10.22270/ajdhs.v1i1.6

56. Nagajyothi PC, Prabhakar Vattikuti S V., Devarayapalli KC, Yoo K, Shim J, Sreekanth TVM. Green synthesis: Photocatalytic degradation of textile dyes using metal and metal oxide nanoparticles-latest trends and advancements. Crit Rev Environ Sci Technol. 2020;50(24):2617-723. https://doi.org/10.1080/10643389.2019.1705103

57. Korkina LG, Afanas'Ev IB. Antioxidant and Chelating Properties of Flavonoids. Adv Pharmacol. 1996;38(C):151-63. https://doi.org/10.1016/S1054-3589(08)60983-7 PMid:8895808

58. Mutha RE, Tatiya AU, Surana SJ. Flavonoids as natural phenolic compounds and their role in therapeutics: an overview. Futur J Pharm Sci. 2021;7(1). https://doi.org/10.1186/s43094-020-00161-8 PMid:33495733 PMCid:PMC7816146

59. Tomazetti J, Ávila DS, Oliveira Ferreira AP, Martins JS, Souza FR, Royer C, et al. Baker yeast-induced fever in young rats: Characterization and validation of an animal model for antipyretics screening. J Neurosci Methods. 2005;147(1):29-35. https://doi.org/10.1016/j.jneumeth.2005.03.002 PMid:16054514

60. Ferreira RT, Coutinho MAS, Malvar DDC, Costa EA, Florentino IF, Costa SS, et al. Mechanisms underlying the antinociceptive, antiedematogenic, and anti-inflammatory activity of the main flavonoid from kalanchoe pinnata. Evidence-based Complement Altern Med. 2014;2014. https://doi.org/10.1155/2014/429256 PMid:25580151 PMCid:PMC4279175

61. Owoyele BV, Oguntoye SO, Dare K, Alice B, Adeola E, Ayodele A, et al. Analgesic, anti-inflammatory and antipyretic activities from flavonoid fractions of Chromolaena odorata. J Med Plants Res. 2013;2(9):219-25.

62. FERNANDES JM. Bryophyllum pinnatum E Kalanchoe laciniata: ESTUDO FITOQUÍMICO, METABOLÔMICO E AVALIAÇÃO DA INIBIÇÃO DA ATIVIDADE FOSFOLIPÁSICA DA PEÇONHA DE Bothrops erythromelas DE EXTRATOS OBTIDOS SOB DIFERENTES CONDIÇÕES DE CULTIVO. Prog Retin Eye Res. 2019;561(3):S2-3.

63. Ball GL, McLellan CJ, Bhat VS. Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: A category approach. Crit Rev Toxicol. 2012;42(1):28-67. https://doi.org/10.3109/10408444.2011.623149 PMid:22050403

64. Salami EO, Ozolua RI, Okpo SO, Eze GI, Uwaya DO. Studies on the anti-asthmatic and antitussive properties of aqueous leaf extract of Bryophyllum pinnatum in rodent species. Asian Pac J Trop Med. 2013;6(6):421-5. https://doi.org/10.1016/S1995-7645(13)60067-X PMid:23711699

65. Mahajan SG, Mehta AA. Effect of Moringa oleifera Lam. Seed extract on ovalbumin-induced airway inflammation in guinea pigs. Inhal Toxicol. 2008;20(10):897-909. https://doi.org/10.1080/08958370802027443 PMid:18686107

66. Carullo G, Cappello AR, Frattaruolo L, Badolato M, Armentano B, Aiello F. Quercetin and derivatives: Useful tools in inflammation and pain management. Future Med Chem. 2017;9(1):79-93. https://doi.org/10.4155/fmc-2016-0186 PMid:27995808

67. Thakur R, Jain N, Pathak R, Sandhu SS. Practices in wound healing studies of plants. Evidence-based Complement Altern Med. 2011;2011. https://doi.org/10.1155/2011/438056 PMid:21716711 PMCid:PMC3118986

68. Alfred S, Kimberlee T. Safety Profile and Effect on Libido of a Combined Bryophyllum pinnatum, Moringa oleifera and Vitamin C Phytotherapeutic Agent. Free Radicals Antioxidants. 2017;7(2):156-9. https://doi.org/10.5530/fra.2017.2.23

69. Pezzati M, Rossi S, Tronchin M, Dani C, Filippi L, Rubaltelli FF. Umbilical cord care in premature infants: the effect of two different cord-care regimens (salicylic sugar powder vs chlorhexidine) on cord separation time and other outcomes. Pediatrics. 2003;112(4). https://doi.org/10.1542/peds.112.4.e275 PMid:14523211

70. Poddar S, Sarkar T, Choudhury S, Chatterjee S, Ghosh P. International Journal of Botany Studies International Journal of Botany Studies Indian traditional medicinal plants: A concise review. WwwBotanyjournalsCom. 2020;5(September).

71. M. P, M. D, S. G, S.K. C. Phytomedicine: An ancient approach turning into future potential source of therapeutics. J Pharmacogn Phyther. 2011;3(2):27-37