Numerous dietary and non-dietary plants have been employed by tribal populations for ethnomedicine purposes based on traditional beliefs or the basis of ancient treatises on Indian, Chinese, Tibetan, Japanese, Korean, and European traditional medicine are all examples of traditional medicine. The medicinal plants are utilised as whole plant extracts or extracts of various sections of the plants, such as leaves, aerial components, roots, stems, rhizomes, or bark. In single herb formulations, the plants are used alone; in polyherbal treatments, they are combined with numerous other plants. Herbs have been a widely used remedy in the search for new agents to prevent and treat a range of acute and chronic ailments. The ancient world serves as a prominent source of research in this field^12,13.

Due to their alleged efficacy and presumed safety, plant-based medications have attracted a lot of attention in modern medicine, particularly for the prevention and treatment of numerous chronic degenerative diseases⁵. Numerous epidemiological, clinical, observational, and meta-analyses of human research have shown a beneficial link between increased intake of fruits and vegetables and a decrease in cancer and cardiovascular disorders. Pharmacologically, the recent increase in the preventive capacity of medicinal plants is mostly attributable to the control of cell death and survival in several organs, including the heart, which mediates powerful free radical scavenging and antioxidant performance. Many of the plant extracts are referred to as antioxidants since it has been demonstrated that they activate the host's protective defence mechanism, which provides defence against the oxidative environment and subsequent immune-inflammatory processes^8,13,14.

Plant-derived antioxidants have recently attracted attention as a way to combat the cardiotoxicity caused by DOX. Since there have been numerous in-depth analyses of DOX-induced cardiotoxicity available elsewhere in the literature in recent years¹⁵. The research on the mechanism of DOX cardiotoxicity and its reversal by antibodies or small synthesised compounds is considerable, according to the reviews that are currently available⁵. Despite multiple studies showing the effectiveness of extracts for cardioprotection against cardiotoxicity, there is not a comprehensive review of the function of various medicinal plant extracts in preventing DOX-associated cardiotoxicity and producing a salubrious effect on the heart^11,13,16. Instead of extrapolating efficacy based on a more generalised antioxidant effect, the number of plants becomes significantly smaller when the inclusion criteria are restricted to include just plants that particularly give protection against DOX¹⁷. The current article lists the cardioprotective effectiveness of numerous naturally occurring plants from various families and genera that have been claimed to have cardioprotective qualities against DOX-induced heart damage, shown in table 2. Plant extracts' therapeutic advantages in preventing cardiotoxicity brought on by DOX are frequently seen as being of added benefit because they also have organ-protective effects on other organs^18,19.

Medicinal Plants Having Salubrious Effect On The Heart Against Dox-Induced Cardiotoxicity:

Leuzea uniflora:

Leuzea uniflora, also referred to as Edelweiss or Alpine Edelweiss, is a perennial herbaceous plant that is a member of the Asteraceae family. Leuzea uniflorous root is the component of the plant that is most frequently utilised for medicinal purposes. Leuzea uniflora root is known to contain a number of biologically active substances, including sesquiterpene lactones, flavonoids, sterols, and polyacetylenes, which are thought to contribute to its possible therapeutic effects. It is indigenous to mountainous areas of Europe and Asia, such as the Alps, Carpathians, Pyrenees, and Himalayas^20,21.

Phytochemical profile:

Leuzeanin A, B, C, and D are examples of sesquiterpene lactones that are found in Leuzea uniflora. It also contains flavonoids like apigenin, quercetin, kaempferol, luteolin, Sterols include campesterol, stigmasterol, and sitosterol. Falcarinol and other polyacetylene phenolic substances, including ferulic acid, chlorogenic acid, and caffeic acid Terpene, sesquiterpene, and alcohol constituents of essential oils²¹.

Actions against Doxorubicin-induced cardiotoxicity:

a)Antioxidant activity:

Leuzea uniflora has been said to possess strong antioxidant capabilities that may work to mitigate the oxidative damage brought on by doxorubicin. Doxorubicin-induced cardiotoxicity involves the production of reactive oxygen species (ROS) in the heart by doxorubicin, which cause oxidative damage to cardiac cells. Leuzea uniflora's antioxidant properties may help scavenge ROS and lessen oxidative stress in the heart, preventing doxorubicin-induced cardiotoxicity²⁰.

b)Anti-inflammatory effects:

It has been discovered that Leuzea uniflora contains anti-inflammatory characteristics, like it inhibits nuclear factor-κB (NF-κB) and chemical mediatiors like IL-1β, prostaglandins, TNF-α, histamine, IL-6, nitric oxide NO, and other cytokines, which may also contribute to its protective action against the cardiotoxicity caused by doxorubicin. Doxorubicin causes heart inflammation, which damages cardiac tissue and impairs cardiac function. Leuzea uniflora has anti-inflammatory properties that may help lessen cardiac inflammation and thereby lessen the cardiotoxic effects of doxorubicin²².

c) Inhibition of apoptosis:

Leuzea uniflora may directly benefit the heart, according to certain studies. It has been suggested that it can enhance cardiac function, lessen myocardial damage, and work against apoptosis (programmed cell death) in cardiac cells by inhibiting of NF-κB, cleaved-PARP [Poly(ADP-ribose)-polymerases], Bax, ROS, cleaved-caspase-3, andcleaved-caspase-9, all of which are crucial components of the apoptosis of cardiac cells caused by doxorubicin²³.

d) Modification of cellular signalling pathways:

Leuzea uniflora has been demonstrated to supress a number of cellular signalling pathways vital for cardiac health, including the Akt and ERK pathways, which are crucial for inflammation, cell survival, apoptosis, and oxidative stress. Leuzea uniflora may offer protection against cardiotoxicity caused by doxorubicin by regulating these pathways²¹.

e) Reduce lipid peroxidation:

Doxorubicin-induced cardiotoxicity is also accompanied by an increase in lipid peroxidation, which produces damaging lipid peroxidation products that can harm cardiac cells. It has been demonstrated that Leuzea uniflora lowers lipid peroxidation, which might help stop doxorubicin-induced cardiotoxicity²⁴.

Cinnamomum zeylanicum Blume:

The cinnamon plant, Cinnamomum zeylanicum Blume (Family Lauraceae), belongs to the Magnoliophyte phylum, class Magnoliopsida, according to the botanical classification. Typically, the south of India is where Cinnamomum zeylanicum is grown. However, it comes from Sri Lanka, previously Ceylon, and an island in the Indian Ocean to the southeast. The centre portion of the bark is dried to produce cinnamon spice, which is sold as powder or quills^25,26.

Phytochemical profile:

The Cinnamomum zeylanicum Blume plant's various sections, including the bark, roots, leaves, flowers, fruit stalks, and buds, produce essential oils with varying chemical compositions like cinnamaldehyde, β-pinene, α-terpinene, D-limonene, eugenol, β-phellandrene, eucalyptol, limonene 1,2 -epoxide, and cinnamyl acetate, that have shown anti-inflammatory, antioxidant, and cardioprotective action against DOX-mediated cardiotoxicity²⁵.

Actions against Doxorubicin-induced cardiotoxicity:

a) Antioxidant activity:

Cinnamomum zeylanicum Blume is recognized for its potent antioxidant properties. The production of reactive oxygen species (ROS) is primarily responsible for doxorubicin-induced cardiotoxicity, resulting in oxidative stress and damage to cardiac tissue. Cinnamon has been found to scavenge ROS and reduce oxidative stress by increasing the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase. These enzymes are crucial to the cellular response to oxidative stress. By stimulating the activity of these enzymes, cinnamon may strengthen the heart's antioxidant defense mechanism and guard against cardiotoxicity brought on by doxorubicin, thus protecting against doxorubicin-induced cardiotoxicity²⁷.

b)Anti-inflammatory activity:

Studies have shown that cinnamon possesses anti-inflammatory properties. This is achieved through various mechanisms such as reducing the mRNA expression of tumour necrosis factor-alpha (TNF-α), inhibiting interlukin-8 (IL-8) signalling, and inhibiting NF-κB by counteracting toll-like receptors 2 and 4 (TLR 2, 4). Inflammation plays a crucial role in the pathogenesis of doxorubicin-induced cardiotoxicity, and cinnamon may help reduce inflammation in the heart tissue, thereby protecting against cardiotoxicity²⁸.

c) Inhibition of lipid peroxidation:

DOX accelerates the formation of ROS and peroxinitrite, which enhances lipid peroxidation, which disrupts the cell membrane integrity in myocardial cells and makes oxidised LDL particles in the blood that cause cardiac inflammation. Cinnamomum zeylanicum Blume extract has multiple phenolic compounds that stimulate antioxidant enzymes like CAT and GPx and reduce the formation of ROS. Eugenol inhibits the lipid peroxidation induced by peroxynitrite²⁹.

Nauclea orientalis:

Nauclea orientalis (Family: Rubiaceae) is a big tree found across in India and is native to Nigeria and north Australia. Cough, cold, stomach ache, vomiting, and diarrhoea are all treated by using a mixture made from seed pulp. The leaf extracts contained angustilobine-type alkaloids and indole alkaloidal glycosides, according to a literature review. There are three of them: two diastereoisomeric 3, 14 -dihydroangustolines and 10-hydroxyangustine. The human breast cancer MCF-7 and murine leukemic cell lines were found to be resistant to these drugs' in vitro antiproliferative activity³⁰.

Phytochemical profile:

According to phytochemical study, several several kinds of chemical compounds have been found in N. officinalis, including phenolic acids, pentacyclic triterpenoids, and alkaloids. The distinguishing features of N. officinalis and its principal active ingredients are alkaloids³¹. The stems and roots were used to produce the majority of these chemicals. Naucleidinal derivatives, such as naucleactonin A, vanillic acid, pumiloside, strictosamide, naucleidinal, 19-epi-naucleidinal, aligenoside, naucleficine, and,sweroside are the primary chemical components of N. orientalis³².

Actions against Doxorubicin-induced cardiotoxicity:

a) Antioxidant properties:

Cardiotoxicity is recognised to be mainly brought on by oxidative stress, and cardiomyocytes are more susceptible to damage if their antioxidant defence mechanism is insufficient. As evidenced by the significantly increasedmalondialdehyde (MDA) concentration and the decreased levels of SOD, GR, GSH, GPx, catalase, and in the DOX control group, oxidative damage was present. However, The water Nauclea bark strain was capable of to significantly increase all the antioxidant enzyme functions in the plant strain-treated group, showing its potent antioxidant properties³³.

b) Anti-inflammatory properties:

Both the proinflammatory cytokine TNF-α, and the inflammatory mediator NO were markedly reduced. It's interesting to note that Nauclea orientalis had no influence on the expression of the COX-2 protein, but it did suppress the up regulation of the inflammatory protein-induced nitric oxide synthase (iNOS). This plant extract supress the exocytosis of inflammatory cytokines namely interleukin 8, interleukin 6,interleukin 1, and TNF-α, which are indicators of inflammation caused on by DOX³⁴.

c) Anti-apoptotic effects:

Apoptosis, or programmed cell death, also contributes significantly to Dox-induced cardiotoxicity by raising cytochrome c, expression of proapoptotic genes and caspases. Dox decreases the production of Bcl-2, a key antiapoptotic protein, and caspase 3 activity, which suppresses apoptosis. According to a study, pretreatment with a bark aqueous extract of the Nauclea orientalis exhibited a significant decrease in caspase-3 activity and increase in Bcl-2 marker expression, indicating that antiapoptotic effect is shown by Nauclea bark³³.

d) Detoxification properties: Nauclea orientalis has been reported to have detoxifying properties, which could potentially help the body eliminate doxorubicin and its toxic metabolites more efficiently, reducing their accumulation in the heart and potentially mitigating cardiotoxicity³⁵.

Scutellaria baicalensis:

Scutellaria baicalensis (family Lamiaceae) that is known for its dried root, often known as skullcap or huangqin. For thousands of years, China and its neighbours have utilized SB extensively. It primarily grows in temperate climates and tropical highlands (at an altitude of roughly 1300–3000m), including China, Japan, Mongolia, North Korea, Eastern Siberia of Russia, and others. It is used for the treatment of bitter, cold, lung, and liver problems³⁶.

Phytochemical profile:

Scutellaria baicalensis has produced more than 40 isolated and recognized components, including polysaccharides, volatile oils, flavonoids, and terpenoids³⁷. The three most notable chemicals discovered in Scutellaria species are baicalin, baicalein, and wogonin³⁸. Among the different substances, baicalein reduced myocardial remodeling and enhanced cardiac performance by altering Ca(2+) handling proteins³⁹. 126 small molecule compounds (1-126) and six polysaccharides have been recognised from S. baicalensis to date. The roots were used to produce the majority of these chemicals. It is having compouns that may be divided into four different structural types: flavonoid glycosides, free flavonoids, phenylethanoid glycosides, and other low molecular weight compounds. Glycosides and flavonoids and are the primary components of Scutellaria baicalensis⁴⁰. It is significant to highlight that several 4′-deoxyflavones, including wogonin, chrysin, baicalein, and their glycosides (baicalin and wogonoside), are responsible for S. baicalensis' pharmacological effects⁴¹.

Actions against Doxorubicin-induced cardiotoxicity:

a) Antioxidant activity:

Baicalin and baicalein are flavonoids obtaining from Scutellaria baicalensis, which have potent antioxidant properties. These compounds can engulf free radicals and mitigate oxidative stress by increasing the level of antioxidant enzymes SOD, GSH, and CAT in the heart, which is one of the main cardioprotective mechanisms of doxorubicin causing cardiotoxicity⁴².

b) Anti-inflammatory effects:

Production and release of numerous inflammatory mediators, including prostaglandins and cytokines (including interleukins and TNF-α), are inhibited when baicalein is present. Additionally, it modifies NF-κB activity. These chemicals are important components of the inflammatory response and can cause damage to heart tissue and produce cardiotoxicity. Baicalein can also stop the formation of inflammatory chemicals like prostaglandins and leukotrienes by inhibiting enzymes like COX and LOX⁴³.

c) Inhibition of lipid peroxidation:

In myocardial cells, DOX speeds up the production of ROS and peroxinitrite, which increases lipid peroxidation and results in oxidised LDL particles that damage cell membrane integrity and lead to heart inflammation. Scutellaria baicalensis contains baicalein, oroxylin A, wogonin, and baicalin, which have high potencies to scavenge free radicals, resulting in a decrease in the generation of oxidised LDL and inhibition of lipid peroxidation⁴⁴.

Citrullus colocynthis:

Citrullus colocynthis, commonly referred to as bitter cucumber or bitter apple, is a plant species belonging to the Cucurbitaceae family. It is native to the Mediterranean region and is also found in various parts of Africa, Asia, and the Middle East. Citrullus colocynthis has a long history of traditional use in herbal medicine for its potential health benefits⁴⁵.

Phytochemical profile:

Citrullus colocynthis, this arid plant has a wide range of bioactive compounds, including glycosides, fatty acids, flavonoids, cucurbitacins A, B, C, D, E, J, L, andalkaloids⁴⁶,. Cucurbitacin, bioactive substances has the ability to prevent cardiac hypertrophy by raising the degree of autophagy in cardiomyocyte^47,48.

Actions against Doxorubicin-induced cardiotoxicity:

a) Antioxidant properties:

DOX has a high affinity for phospholipids in myocardial cells, and its metabolite DOX-semiquinone, that interacts with oxygen (O2) molecules to form H2O2 and O2 (superoxide), enhances oxidative damage in myocardium. Additionally, it increases the formation of xanthine and NADPH oxidase, inhibits the transfer of iron, which produces ROS as a result. Extract from C. colocyn leaves revealed that it includes phenols, tannins, alkaloids, glycosides, flavonoids, saponins, saponins, steroids, and flavonoids. It's believed that these phytochemicals are actually reduces the oxidative stress imposed on by DOX. The study also revealed that the extract also reduces the lactate dehydrogenase, a key enzyme for inflammation⁴⁹.

b) Anti-inflammatory properties:

An intraplantar injection of carrageenan increases the expression and release of a number of cytokines, including TNF-α and Interlukin-1 (IL-1), which in turn triggers the release of additional pro-inflammatory mediators, such as leukotrienes, Interlukin-6 (IL-6), arachidonic acid metabolites, kinins, and reactive oxygen species. These proinflammatory cytokines in the heart causes myocardial inflammation⁵⁰. A study in 2015, revealed that treatment with an ethanol extract of C. colocyn decreased the biosynthesis of various pro-inflammatory mediators such TNF-α, INOS, and COX-2 in macrophages⁵¹.

Persea americana:

Avocado, the common name of Persea americana, is a tree indigenous to Central America and Mexico. It is Lauraceae family member and is known for its distinctive fruit, which is often used in culinary applications around the world. The avocado fruit is prized for its creamy texture, rich flavour, and high nutritional value, and it is commonly used in dishes such as guacamole, salads, sandwiches, and smoothies⁵².

Phytochemical profile:

The plant contains Alkanols (also known as "aliphatic acetogenins"), terpenoid glycosides, coumarin, flavonoids, and various furan ring-containing derivatives. One study obtained 1,2,4-trihydroxyheptadec-16-yne, 1,2,4-trihydroxyheptadec-16-ene, and 1,2,4-trihydroxynonadecane from the immature fruits of P. americana. The majority of the phenolic chemicals in avocado seeds include hydroxybenzoic acid, coumaric acid, caffeic acid, catechin, ferulic acid, and chlorogenic acid^53,54. Phenolic compounds mainly showed cardioprotective activities⁵⁵.

Actions against Doxorubicin-induced cardiotoxicity:

a) Antioxidant properties:

Persea americana contains various bioactive compounds, including polyphenols, carotenoids, and tocopherols, which exhibit antioxidant activity. These compounds can scavenge free radicals and reduce oxidative stress. P. americana contains sitosterol, campesterol, and stigmasterol, which reduce the formation of ROS while attenuating excitotoxicity, mitochondrial malfunction, and mutations in DNA. Antioxidant enzymes, including nitric oxide synthase enzymes (iNOS and nNOS), superoxide dismutase (SOD), and catalase (CAT), all had their activity increased by stigmasterol. Which is known to play a role in doxorubicin-induced cardiotoxicity⁵⁶.

b) Anti-inflammatory properties:

The nuclear factor kappa B (NF-κB), the mitogen-activated protein kinase (MAPK), and the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways are only a few of the cellular signalling pathways that have been proven to be modulated by Persea americana and are important for heart health. Persea americana may have protective effects against the cardiotoxicity caused by doxorubicin by modulating these pathways, which are important in cell survival, oxidative stress, and inflammation^57,58.

c) Cardioprotective effects:

When compared to control groups, acute intraperitoneal injections of DOX produced statistically significant rises in the cardiac risk index values. But there were substantial dose-related reductions in the CRI values with oral pretreatment with extract containing stigmasterol at 100–400mg/kg/day⁵⁹.

CONCLUSION:

This review compiles the most recent information on some plans and mushrooms that are found in nature and drug formulations that offer cardioprotection against DOX-induced cardiotoxicity. The natural resources that have cardioprotective properties may be investigated for their potential use as a preventative measure before the start of therapy or as an adjuvant in treatment. It will be crucial to promote the use of these extracts for additional therapies by being aware of their chemosensitizing ability. The extract may be a novel adjunctive strategy to offer better therapeutic potential in the modulation of the pathogenic process of cardiomyocyte cell death and improving cardiac function in patients with cardiomyopathy, taking into account the multi-target and multicomponent action strategies of natural products. On the other hand, the identification and isolation of phytochemicals in plants and the use of their chemical framework for additional synthesis, design, and development of molecules may hold promise for future treatments that have the capacity to alter signalling mechanisms and provide cardioprotection. Nevertheless, multiple investigations in both in vitro and in vivo settings have shown protection against DOX-induced cardiotoxicity. Some of them, meanwhile, did not translate in vivo despite exhibiting efficacy in vitro. This indicates that either the pro-oxidant function of plants as a toxicity effector was constrained in those tests or the extract is insufficient to effectively combat oxidative stress in this system. However, in the development of natural cardioprotective drugs, these natural resources play a key role in the future that can counteract the cardiotoxicity caused by DOX.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this review.

ACKNOWLEDGMENTS:

The authors would like to thank Dr. Arin Bhattacharjee, Principal, Global College of Pharmaceutical Technology, for his kind support during the search for the literature review.

REFERENCES:

1. McGowan, J. V.; Chung, R.; Maulik, A.; Piotrowska, I.; Walker, J. M.; Yellon, D. M. Anthracycline Chemotherapy and Cardiotoxicity. Cardiovascular Drugs and Therapy. 2017; 31(1): 63-75. doi: 10.1007/S10557-016-6711-0

2. Frengki, Deddi P. Putra, Fatma Sri Wahyuni, Daan Khambri, Vivi Sofia. The effect of Deoxyelephantopin enhances Doxorubicin Sensitivity to MCF-7 Cancer Cells. Research Journal of Pharmacy and Technology. 2021; 14(5): 27915. doi: 10.52711/0974-360X.2021.00492

3. C. Pereira, G.; M. Silva, A.; V. Diogo, C.; S. Carvalho, F.; Monteiro, P.; J. Oliveira, P. Drug-Induced Cardiac Mitochondrial Toxicity and Protection: From Doxorubicin to Carvedilol. Current Pharmaceutical Design. 2011; 17(20): 2113–2129. doi: 10.2174/138161211796904812

4. Akheruz Z. Ahmed, Prakashchandra Shetty, Shakta M. Satyam, Melanie Rose D’Souza, Archana M Herle, Varun K. Singh. Methyl Gallate Mitigates Doxorubicin-Induced Peripheral Cytopenias: A Preclinical Experimental Study. Research Journal of Pharmacy and Technology. 2021; 14(9): 4529-4. doi: 10.52711/0974-360X.2021.00788

5. Ojha, S.; Al Taee, H.; Goyal, S.; Mahajan, U. B.; Patil, C. R.; Arya, D. S.; Rajesh, M. Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity. Oxidative Medicine and Cellular Longevity. 2016; 2016: 5724973. doi: 10.1155/2016/5724973

6. P. Aruna, N. M. Gayathiri. Cardioprotective Activity of Telmisartan, Metformin and its Combination against Doxorubicin Induced Myocardial Infarction in Rat Model. Research Journal of Pharmacy and Technology. 2018; 11(12): 5293-5296. doi: 10.5958/0974-360X.2018.00964.2

7. Mir, A.; Badi, Y.; Bugazia, S.; Nourelden, A. Z.; Fathallah, A. H.; Ragab, K. M.; Alsillak, M.; Elsayed, S. M.; Hagrass, A. I.; Bawek, S.; Kalot, M.; Brumberger, Z. L. Efficacy and Safety of Cardioprotective Drugs in Chemotherapy-Induced Cardiotoxicity: An Updated Systematic Review and Network Meta-Analysis. Cardio-Oncology. 2023; 9(1): 1-34. doi: 10.1186/S40959-023-00159-0

8. Kalam, K.; Marwick, T. H. Role of Cardioprotective Therapy for Prevention of Cardiotoxicity with Chemotherapy: A Systematic Review and Meta-Analysis. European Journal of Cancer. 2013; 49(13): 2900–2909. doi: 10.1016/J.EJCA.2013.04.030

9. QuanJun, Y.; GenJin, Y.; LiLi, W.; YongLong, H.; Yan, H.; Jie, L.; JinLu, H.; Jin, L.; Run, G.; Cheng, G. Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study. PLoS One. 2017; 12(1). doi:10.1371/JOURNAL.PONE.0169567

10. Bachheti, R. K.; Worku, L. A.; Gonfa, Y. H.; Zebeaman, M.; Deepti; Pandey, D. P.; Bachheti, A. Prevention and Treatment of Cardiovascular Diseases with Plant Phytochemicals: A Review. Evidence-Based Complementary and Alternative Medicine. 2022; 2022: 5741198. doi:10.1155/2022/5741198

11. Aithamraju Satish Chandra, P. Shanmugapandiyan. Cardioprotective efficacy of Tridax procumbens methanolic extract in Doxorubicin induced Oxidative Cardiac Damage. Research Journal of Pharmacy and Technology. 2020; 13(1): 110-113. doi: 10.5958/0974-360X.2020.00022.0

12. Lohakul, J.; Chaiprasongsuk, A.; Jeayeng, S.; Saelim, M.; Muanjumpon, P.; Thanachaiphiwat, S.; Tripatara, P.; Soontrapa, K.; Lumlerdkij, N.; Akarasereenont, P.; Panich, U. The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense. Frontiers in Pharmacology. 2021; 12: 649820. doi: 10.3389/FPHAR.2021.649820

13. Viani Anggi, Wirawan Adikusuma. Total Antioxidant and In-Vitro Cytotoxic of Abelmoschus Manihot (L.) Medik from palu of Central Sulawesi and Doxorubicin on 4T1 cells line and Vero Cells. Research Journal of Pharmacy and Technology. 2019; 12(11): 5472-5476. doi: 10.5958/0974-360X.2019.00949.1

14. Zhao, M. Q.; Wu, W. K.; Zhao, D. Y.; Liu, Y.; Liu, Y.; Liang, T. W.; Luo, H. C. [Protective Effects of Sini Decoction on Adriamycin-Induced Heart Failure and Its Mechanism: Role of Superoxide Dismutase]. Zhongguo Zhong Yao Za Zhi. 2005; 30(14): 1111–1114

15. Angsutararux, P.; Luanpitpong, S.; Issaragrisil, S. Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress. Oxidative Medicine and Cellular Longevity. 2015; 2015: 795602. doi: 10.1155/2015/795602

16. VKK Mandlem, N. Gouri Priya, M. Raghavendra, K. Abbulu. Evaluation of Cardioprotective Activity of Tamarindus indica Linn Pericarpic extract in Doxorubicin induced Cardiotoxicity in Experimental Rats. Research Journal of Pharmacy and Technology. 2020; 13(7): 3267-3273. doi: 10.5958/0974-360X.2020.00579.X

17. Adegbola, P.; Aderibigbe, I.; Hammed, W.; Omotayo, T. Antioxidant and Anti-Inflammatory Medicinal Plants Have Potential Role in the Treatment of Cardiovascular Disease: A Review. American Journal of Cardiovascular Disease. 2017; 7(2): 19-32.

18. Shah, S. M. A.; Akram, M.; Riaz, M.; Munir, N.; Rasool, G. Cardioprotective Potential of Plant-Derived Molecules: A Scientific and Medicinal Approach. Dose-Response. 2019; 17(2): 1559325819852243. doi: 10.1177/1559325819852243

19. Divya B, Shivashree S, K. Mruthunjaya, S. N. Manjula. Cardioprotective activity of Lawsonia inermis roots against Doxorubicin Treated Mice. Research Journal of Pharmacy and Technology. 2020; 13(7): 3279-3283. doi: 10.5958/0974-360X.2020.00581.8

20. Kokoska, L.; Janovska, D. Chemistry and Pharmacology of Rhaponticum Carthamoides: A Review. Phytochemistry. 2009; 70(7): 842–855. https://doi.org/10.1016/J.PHYTOCHEM.2009.04.008

21. Olennikov, D. N. The Ethnopharmacological Uses, Metabolite Diversity, and Bioactivity of Rhaponticum Uniflorum (Leuzea Uniflora): A Comprehensive Review. Biomolecules. 2022; 12(11): 1720. doi: 10.3390/BIOM12111720

22. Jeong, Y. H.; Oh, Y. C.; Cho, W. K.; Yim, N. H.; Ma, J. Y. Anti-Inflammatory Effect of Rhapontici Radix Ethanol Extract via Inhibition of NF-ΚB and MAPK and Induction of HO-1 in Macrophages. Mediators of Inflammation. 2016; 2016: 7216912. doi:10.1155/2016/7216912

23. Hu, B.; Zhen, D.; Bai, M.; Xuan, T.; Wang, Y.; Liu, M.; Yu, L.; Bai, D.; Fu, D.; Wei, C. Ethanol Extracts of Rhaponticum Uniflorum (L.) DC Flowers Attenuate Doxorubicin-Induced Cardiotoxicity via Alleviating Apoptosis and Regulating Mitochondrial Dynamics in H9c2 Cells. Journal of Ethnopharmacology. 2022; 288: 114936. doi:10.1016/j.jep.2021.114936

24. Toropova, A. A.; Razuvaeva, Y. G.; Olennikov, D. N.; Markova, K. V.; Lemza, S. V. Protective Effects of Leuzea Uniflora (Rhaponticum Uniflorum) on the Brain Mitochondrial Function in White Rats at Hypoxia/Reoxygenation. Natural Product Research. 2023; 1-6. doi:10.1080/14786419.2022.2155646

25. Denkova-Kostova, R.; Teneva, D.; Tomova, T.; Goranov, B.; Denkova, Z.; Shopska, V.; Slavchev, A.; Hristova-Ivanova, Y. Chemical Composition, Antioxidant and Antimicrobial Activity of Essential Oils from Tangerine (Citrus Reticulata L.), Grapefruit (Citrus Paradisi L.), Lemon (Citrus Lemon L.) and Cinnamon (Cinnamomum Zeylanicum Blume). Zeitschrift für Naturforschung C. 2020; 76(5–6): 175–185. doi:10.1515/znc-2020-0126

26. Kavita Munjal, Vinod Gauttam, Sumeet Gupta, Apeksha Gupta, Lubna Abidin, Vikas Jhawat, Aayeena Altaf. Traditional uses and Phytochemistry of Cinnamomum Species – A Mini Review. Research Journal of Pharmacy and Technology. 2022; 15(11): 5363-7. doi: 10.52711/0974-360X.2022.0090

27. Swamy, A. V.; Gulliaya, S.; Thippeswamy, A.; Koti, B. C.; Manjula, D. V. Cardioprotective Effect of Curcumin against Doxorubicin-Induced Myocardial Toxicity in Albino Rats. Indian Journal of Pharmacology. 2012; 44(1): 73-77. doi:10.4103/0253-7613.91871

28. Schink, A.; Naumoska, K.; Kitanovski, Z.; Kampf, C. J.; Fröhlich-Nowoisky, J.; Thines, E.; Pöschl, U.; Schuppan, D.; Lucas, K. Anti-Inflammatory Effects of Cinnamon Extract and Identification of Active Compounds Influencing the TLR2 and TLR4 Signaling Pathways. Food and Function Journal. 2018; 9(11): 5950-5964. doi:10.1039/c8fo01286e

29. Shang, C.; Lin, H.; Fang, X.; Wang, Y.; Jiang, Z.; Qu, Y.; Xiang, M.; Shen, Z.; Xin, L.; Lu, Y.; Gao, J.; Cui, X. Beneficial Effects of Cinnamon and Its Extracts in the Management of Cardiovascular Diseases and Diabetes. Food and Function Journal. 2021; 12(24): 12194-12220.doi:10.1039/d1fo01935j

30. Raghavamma, S. T. V.; Rao, N. R. In Vitro Evaluation of Anthelmintic Activity of Nauclea Orientalis Leaves. Indian Journal of Pharmaceutical Sciences. 2010; 72(4): 520–521. doi: 10.4103/0250-474X.73932

31. Liu, B.; Geng, Q.; Cao, Z.; Li, L.; Lu, P.; Lin, L.; Yan, L.; Lu, C. Nauclea Officinalis: A Chinese Medicinal Herb with Phytochemical, Biological, and Pharmacological Effects. Chinese Medicine. 2022; 17(1): 141. doi:10.1186/s13020-022-00691-8

32. Sichaem, J.; Worawalai, W.; Tip-Pyang, S. Chemical Constituents from the Roots of Nauclea Orientalis. Chemistry of Natural Compounds. 2012; 48(5): 827–830.doi: 10.1007/S10600-012-0393-Z

33. Sandamali, J. A. N.; Hewawasam, R. P.; Jayatilaka, K. A. P. W.; Mudduwa, L. K. B. Nauclea Orientalis (L.) Bark Extract Protects Rat Cardiomyocytes from Doxorubicin-Induced Oxidative Stress, Inflammation, Apoptosis, and DNA Fragmentation. Oxidative Medicine and Cellular Longevity. 2022; 2022: 1714841. doi:10.1155/2022/171484

34. Song, S.; Liu, P.; Wang, L.; Li, D.; Fan, H.; Chen, D.; Zhao, F. In Vitro Anti-Inflammatory Activities of Naucleoffieine H as a Natural Alkaloid from Nauclea Officinalis Pierrc Ex Pitard, through Inhibition of the INOS Pathway in LPS-Activated RAW 264.7 Macrophages. Natural Product Research. 2020; 34(18): 2694-2697. doi:10.1080/14786419.2018.1550765

35. Chen, Y.; Shi, S.; Dai, Y. Research Progress of Therapeutic Drugs for Doxorubicin-Induced Cardiomyopathy. Biomedicine and Pharmacotherapy. 2022; 156: 113903. doi:10.1016/j.biopha.2022.113903

36. Chang, W. T.; Li, J.; Haung, H. H.; Liu, H.; Han, M.; Ramachandran, S.; Li, C. Q.; Sharp, W. W.; Hamann, K. J.; Yuan, C. S.; Hoek, T. L. V.; Shao, Z. H. Baicalein Protects against Doxorubicin-Induced Cardiotoxicity by Attenuation of Mitochondrial Oxidant Injury and JNK Activation. Journal of Cellular Biochemistry. 2011; 112(10): 2873-2881.doi:10.1002/jcb.23201

37. Zhao, T.; Tang, H.; Xie, L.; Zheng, Y.; Ma, Z.; Sun, Q.; Li, X. Scutellaria Baicalensis Georgi. (Lamiaceae): A Review of Its Traditional Uses, Botany, Phytochemistry, Pharmacology and Toxicology. Journal of Pharmacy and Pharmacology. 2019; 71(9): 1353-1369.doi:10.1111/jphp.13129

38. Shah, M.; Mubin, S.; Ul Hassan, S. S.; Tagde, P.; Ullah, O.; Rahman, M. H.; Al-Harrasi, A.; Ur Rehman, N.; Murad, W. Phytochemical Profiling and Bio-Potentiality of Genus Scutellaria: Biomolecules. 2022; 12(7): 936. doi:10.3390/biom12070936

39. Zhao, F.; Fu, L.; Yang, W.; Dong, Y.; Yang, J.; Sun, S.; Hou, Y. Cardioprotective Effects of Baicalein on Heart Failure via Modulation of Ca(2+) Handling Proteins in Vivo and in Vitro. Life Sciences. 2016; 145: 213-223. doi:10.1016/j.lfs.2015.12.036

40. Wang, Z. L.; Wang, S.; Kuang, Y.; Hu, Z. M.; Qiao, X.; Ye, M. A Comprehensive Review on Phytochemistry, Pharmacology, and Flavonoid Biosynthesis of Scutellaria Baicalensis. Pharmaceutical Biology. 2018; 56(1): 465-484. doi:10.1080/13880209.2018.1492620

41. Song, J. W.; Long, J. Y.; Xie, L.; Zhang, L. L.; Xie, Q. X.; Chen, H. J.; Deng, M.; Li, X. F. Applications, Phytochemistry, Pharmacological Effects, Pharmacokinetics, Toxicity of Scutellaria Baicalensis Georgi. and Its Probably Potential Therapeutic Effects on COVID-19: A Review. Chinese Medicine. 2020; 15: 20. doi: 10.1186/S13020-020-00384-0

42. Hana Bajes, Sawsan Oran, Yasser Bustanji. Phytochemical Analysis, In vitro Assessment of Antioxidant Properties and Cytotoxic Potential of Thymus capitatus Essential Oil. Research Journal of Pharmacy and Technology. 2023; 16(3): 1100-8. doi: 10.52711/0974-360X.2023.00183

43. Li, B. Q.; Fu, T.; Gong, W. H.; Dunlop, N.; Kung, H. F.; Yan, Y.; Kang, J.; Wang, J. M. The Flavonoid Baicalin Exhibits Anti-Inflammatory Activity by Binding to Chemokines. Immunopharmacology. 2000; 49(3): 295-306. doi:10.1016/s0162-3109(00)00244-7

44. Liau, P. R.; Wu, M. S.; Lee, C. K. Inhibitory Effects of Scutellaria Baicalensis Root Extract on Linoleic Acid Hydroperoxide-Induced Lung Mitochondrial Lipid Peroxidation and Antioxidant Activities. Molecules. 2019; 24(11): 2143. doi:10.3390/molecules24112143

45. Ahmed, Maqsood and Sikandar, Aatika and Iqbal, Mazher Farid and Javeed, Ansar and ji, Mingshan and Peiwen, Qin and liu, Yuyang and Gu, Zumin. Phytochemical screening, Total phenolics and Flavonoids content and Antilxidant Activities of Citrullus colocynthis L. and Cannabis sativa L. Applied Ecology and Environmental Research. 2019; 17: 6961-6979. doi: 10.15666/aeer/1703_69616979

46. Li, Q. Y.; Munawar, M.; Saeed, M.; Shen, J. Q.; Khan, M. S.; Noreen, S.; Alagawany, M.; Naveed, M.; Madni, A.; Li, C. X. Citrullus Colocynthis (L.) Schrad (Bitter Apple Fruit): Promising Traditional Uses, Pharmacological Effects, Aspects, and Potential Applications. Frontiers in Pharmacology. 2022; 12: 791049. doi:10.3389/fphar.2021.791049

47. Xiao, Y.; Yang, Z.; Wu, Q. Q.; Jiang, X. H.; Yuan, Y.; Chang, W.; Bian, Z. Y.; Zhu, J. X.; Tang, Q. Z. Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy. Journal of Cellular Biochemistry. 2017; 118(11): 3899-3910. doi:10.1002/jcb.26041

48. Jeong, M. H.; Kim, S. J.; Kang, H.; Park, K. W.; Park, W. J.; Yang, S. Y.; Yang, D. K. Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2) and TGF- β/Smads Signalings. PLoS One. 2015; 10(8): e0136236. doi: 10.1371/journal.pone.0136236

49. Manzoor, A.; Khan, I. A.; Sadiq, M.; Iqbal, M. O.; Munawar, S. H. Evaluation of Cardioprotective Potential of Hydroalcoholic Leaf Extract of Citrullus Colocynthis against Doxorubicin Induced Oxidative Stress in Rats. Pakistan Journal of Zoology. 2023; 55(1): 193–200. doi: 10.17582/JOURNAL.PJZ/20210715090741

50. Murray, A. R.; Kisin, E.; Castranova, V.; Kommineni, C.; Gunther, M. R.; Shvedova, A. A. Phenol-Induced in Vivo Oxidative Stress in Skin: Evidence for Enhanced Free Radical Generation, Thiol Oxidation, and Antioxidant Depletion. Chemical Research in Toxicology. 2007; 20(12): 1769-1777. doi:10.1021/tx700201z

51. Akhzari, M.; S, M. M.; Vassaf, M.; Bidgoli, M. S. M.; Tari, Z. S. The Effect of Citrullus Colocynthis on the Reduction of InflammatoryAgents in Osteoarthritis. Molecular Biology. 2015; 4(4): 1-6. doi: 10.4172/2168-9547.1000147

52. Zeena Fernandes, Prasanna Shama Khandige, Ullas Prakash D’Souza. Anxiolytic potential of Perseaamericana M. by elevated plus maze test. Research Journal of Pharmacy and Technology. 2020; 13(7): 3326-3328. doi: 10.5958/0974-360X.2020.00590.9.

53. Setyawan, H. Y.; Sukardi, S.; Puriwangi, C. A. Phytochemicals Properties of Avocado Seed: A Review. IOP Conference Series: Earth and Environmental Science. 2021; 733(1): 012090. Doi: 10.1088/1755-1315/733/1/012090

54. Yasir, M.; Das, S.; Kharya, M. The Phytochemical and Pharmacological Profile of Persea Americana Mill. Pharmacognosy Reviews. 2010; 4(7): 77-84. doi:10.4103/0973-7847.65332

55. Razavi-Azarkhiavi, K.; Iranshahy, M.; Sahebkar, A.; Shirani, K.; Karimi, G. The Protective Role of Phenolic Compounds Against Doxorubicin-Induced Cardiotoxicity: A Comprehensive Review. Nutrition and Cancer. 2016; 68(6): 892-917. doi:10.1080/01635581.2016.1187280

56. Kumar, Gaurav and Mukherjee, Sumedha and Patnaik, Ranjana. Identification of Withanolide-M and Stigmasterol as Potent neuroprotectant and Dual inhibitor of Inducible/Neuronal Nitric Oxide Synthase by Structure-Based Virtual Screening. Journal of Biological Engineering Research and Review. 2017; 4: 9-13

57. Bakrim, S.; Benkhaira, N.; Bourais, I.; Benali, T.; Lee, L. H.; El Omari, N.; Sheikh, R. A.; Goh, K. W.; Ming, L. C.; Bouyahya, A. Health Benefits and Pharmacological Properties of Stigmasterol. Antioxidants. 2022; 11(10): 1912. doi:10.3390/antiox11101912

58. Zeena Fernandes. In Vitro Anti Inflammatory Activity on the Ethanolic bark extract of Perseaamericana M. Research Journal of Pharmacy and Technology. 2018; 11(12): 5517-5519. doi: 10.5958/0974-360X.2018.01004.1

59. Olorundare, O.; Adeneye, A.; Akinsola, A.; Kolo, P.; Agede, O.; Soyemi, S.; Mgbehoma, A.; Okoye, I.; Albrecht, R.; Mukhtar, H. Irvingia Gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats. Oxidative Medicine and Cellular Longevity. 2020; 2020: 1602816. doi:10.1155/2020/1602816

Received on 21.08.2023 Modified on 14.11.2023

Research J. Pharm. and Tech 2024; 17(6):2933-2942.

DOI: 10.52711/0974-360X.2024.00459

Common name	Scientific name and Family	Parts used	Chemical constituents	Mechanism of attenuating DOX-induced cardiotoxicity	References
Edelweiss or Alpine Edelweiss	Leuzea uniflora (Asteraceae)	Roots	Flavonoids like Leuzeanin A, B, C, and D, sterols, others polyacetylenephenolic substance and alcoholic constituents of essential oils.	Antioxidant, Anti-inflammatory, Modification of cellular signaling pathways, Reduce lipid peroxidation.	20-24
Cinnamon plant	Cinnamomum zeylanicum Blume Lauraceae	Barks,roots, leaves, flowers, fruit stalks, and buds	Essential oils like cinnamaldehyde, β-pinene, α-terpinene, D-limonene, eugenol, β-phellandrene, eucalyptol, limonene 1,2 -epoxide, and cinnamyl acetate	Antioxidant, anti-inflammatory, and Inhibition of lipid peroxidation	25-29
Yellow Cheesewood	Nauclea orientalis Rubiaceae	Roots	Derivatives of Naucleidinal such as naucleactonin A, vanillic acid, pumiloside, strictosamide, naucleidinal, 19-epi-naucleidinal, aligenoside, naucleficine, and,sweroside	Antioxidant, Anti-inflammatory, Anti-apoptotic effects, and Detoxification properties	30-35
Skullcap or Huangqin	Scutellaria baicalensis Lamiaceae	Dried roots	4′-Deoxyflavones including chrysin, baicalein, wogonin, and their glycosides (baicalin and wogonoside)	Antioxidant, anti-inflammatory, and Inhibition of lipid peroxidation	36-44
Bitter cucumber or Bitter apple	Citrullus colocynthis Cucurbitaceae	Dried fruit pulps, root, seeds, leaves	Bioactive substances, including fatty acids, cucurbitacins A, B, C, D, E, J, L glycosides, flavonoids, and alkaloids	Antioxidant, and Anti-inflammatory	45-51
Avocado	Persea Americana Lauraceae	Leaves, Unripe fruit, seeds,bark	Terpenoid glycosides, coumarin, flavonoids, and various furan ring-containing derivatives.	Antioxidant,Cardioprotective effects and Anti-inflammatory	52-59