Antiparasitic potential of plant natural products against protozoans, nematodes and cestodes: A review

Review Article | DOI: https://doi.org/10.31579/2639-4162/140

Antiparasitic potential of plant natural products against protozoans, nematodes and cestodes: A review

  • Ravi Kant Upadhyay *

Department of Zoology D D U Gorakhpur University, Gorakhpur, 273009. U.P. India

*Corresponding Author: Ravi Kant Upadhyay, Department of Zoology D D U Gorakhpur University, Gorakhpur, 273009. U.P. India.

Citation: Ravi Kant Upadhyay, (2024), Antiparasitic Potential of plant Natural Products against Protozoans, Nematodes and Cestodes: A Review, J. General Medicine and Clinical Practice, 7(6); DOI:10.31579/2639-4162/140

Copyright: © 2024, Ravi Kant Upadhyay. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 08 January 2024 | Accepted: 29 February 2024 | Published: 26 March 2024

Keywords: plant natural products; antiparasitic potential; protozoans; nematodes and cestodes

Abstract

This review article discusses the potential of plant-based remedies against protozoans, nematodes and cestodes. Plant natural products show the ability to kill parasites, reduce the morbidity and mortality of hosts. These parasites are a major threat to the health of humans and animals, as well as causing huge economic losses. For fighting dreadful parasites Garlic (Allium sativum) contains sulfur-containing compounds allicin, flavonoid glycosides in C. viscose, aloe-emodin from Aloe vera, azadirachtin, from Neem Azedarach indica, are widely used in traditional medicine. Toddalia asiatica contain coumarins and alkaloids which display strong anti-parasitic activity, Curcumin is a polyphenolic major active ingredient obtained from rhizome of turmeric the Curcuma longa L. It exhibits a wide range of pharmacological activities including anti-parasitic effect. Beside above components plant latex, gums and other natural products also showed antiparasitic activity. This plant-based remedy is widely used in control of intestinal parasites and cellular protozoans.

Introduction

Table 1: Showing various plant species with anti-parasitic potentialParasites rely on hosts to obtain nourishment for their survival. They invade host and establish their life cycle to reproduce and generate future progenies.  They reach inside host body through contaminated water, food, utilizable and through vector bites. There are three main classes of parasites that can cause disease in humans: protozoa, helminths, and ectoparasites. The helminths are worm-like parasites. There are both hermaphroditic and bisexual species.  These are invertebrates characterized by elongated, flat or round bodies. Intestinal helminthic infection is most common infection in tropical and subtropical countries [1]. These groups are subdivided for convenience according to the host organ in which they reside, e.g., lung flukes, extra-intestinal tapeworms, and intestinal roundworms. The main types of helminths that affect people include flukes, tapeworms and round worms. Helminthic parasites multiply enormously inside human intestine and cause anemia. These effect health by hindering growth and stop mental development. These stay inside host intestine and incalculable economic losses.Till the date 342 helminth species are known which infect humans [2]. Platyhelminths are flatworms mainly flukes and tapeworms invade gastrointestinal tract. Flukes (trematodes) are a type of flatworm.  They possess prominent oral and ventral suckers help maintain position in situ. Flukes are hermaphroditic except for blood flukes, which are bisexual. The life-cycle includes a snail intermediate host. Second category is tapeworms (cestodes). These are elongated, segmented, hermaphroditic flatworms that inhabit the intestinal lumen. Larval forms, which are cystic or solid, inhabit extra-intestinal tissues. Ascaris, roundworms or eelworms are nematodes which inhabit in a broad range of environments. Roundworms are nematodes (which pass on their life cycle in different hosts as egg, larva and adults. These are bisexual, cylindrical worms. They inhabit intestinal and extraintestinal sites. Most species are free-living, feeding on microorganisms, but there are many that are parasitic. These worms are responsible for chronic infections often lead to severe manifestations, such as malnutrition, anemia, stunted growth, poor intellectual development, etc., particularly in children [3]. Though there are some safe and effective anthelminthic drugs to treat the intestinal helminths, the greatest challenge is to extend regular anthelminthic drug coverage to reach all the individuals in endemic areas [4].The most common intestinal parasites are Ascaris lumbricoides (roundworm), Cyclostome duodenale and Nicator americanus (hookworms), Trichuris trichiurid (whipworm), Enterobius vermicularis (pinworm) and Strongyloidiasis stercoral is (threadworm). They essentially need their host for their survival. For this reason, they rarely kill their host, but they often carry diseases that can be life-threatening. Gastrointestinal (GI) parasitic infections not only affect humans but also dairy severely affect health of livestock and hit dairy in tropical and subtropical countries. These effectively cut down production of meat, milk, and enhance susceptibility to diseases. Intestinal schistosomiasis is caused by Schistosoma mansion. This is a water-borne parasite of humans, and belongs to the group of blood flukes. The adult Schistosomes reside in the blood vessels near the human intestine. It is one of most dreadful helminthic infections as the approximate number of active cases remains between 391 and 587 million people worldwide. It imposes a global disease burden as the loss of ability in 24–56 million life years loss [5]. For treatment only a single drug is available praziquantel against which parasite has developed resistance [6]. No vaccine is available to treat this resistant schistosome infection, but certain plant natural products show much diverse antiparasitic activity against Schistosomiasis [7-9]. Nematodes heavily take upon cattle and infest them very massively. Hence control of nematodes various chemical anthelmintics are used [10]. These chemicals are toxic and generally expensive. Due to repetitive use helminth parasites have developed of resistance in to various anthelmintic compounds [11] and chemical residue and toxicity problems [12]. To replace these harmful chemicals various medicinal plants have been screened for their anthelmintic activity remains of great scientific interest [13]. For control of infection of parasites prophylactic, sanitary and good hygiene should be practiced. Keep children away from garbage, contaminated soil, dirty water and foul-smelling areas. Always wash vegetables with saline water to kill eggs and larvae of parasites, eat properly cooked meat and intake cleaned drinking water. Besides, this vector control is also highly essential to control the transmission of infection.

Protozoans are eukaryotic, unicellular, heterotrophic organisms that can be either parasites or free-living. They exhibit an enormous range of morphologies and lack cell walls, for example, Entamoeba, Plasmodium, Paramecium, etc. Protozoan live inside host’s blood stream where they damage blood cells, grow and multiply. These are transmitted by various species of flies and mosquitoes. Many important human and animal diseases are caused by protozoans [14]. In addition to being known as parasites, some protozoa are considered opportunistic pathogens that primarily affect immunocompromised individuals. There are protozoans which cause malaria, filarial, African sleeping sickness, amoebic dysentery while animal Leishmaniasis (dogs, humans and rodents), Babesiosis, etc. There are five most prominent protozoan diseases. Malaria is caused by four different species of Plasmodium. It is a mosquito-borne protozoan infectious disease that affects both animals and humans. Trypanosomiasis is a disease that is caused by different species of Trypanosoma a flagellate protozoan that resides in blood and affects lymph gland, aching muscles, fever, pain in joints. Amoebiasis is a protozoan infection protozoan Entamoeba histolytica. It causes severe weight loss, diarrhea, abdominal pain, colonic ulcerations and even bloody diarrhea that causes anemia [15]. Leishmaniasis is caused by more than twenty Leishmania species. Parasite evokes fever, skin ulcers, and enlarged liver and low red blood cells. 

Data collection and source of information:

For writing this comprehensive research review various electronic databases were searched, using keywords, anti-parasitic activities of plants and plant natural products. For collection of relevant information specific terms such as medical subject headings (Mesh) and key text words, such as anti-parasitic term was used in MEDLINE and electronic data was excavated up to December 2023. Plant species which exhibited antihelminth and anti-protozoan activity were oted. Most specially for retrieving all articles pertaining to the traditional uses of plant natural products for parasite killing various electronic bibliographic databases were searched and abstracts of published studies with relevant information on various species of Hibiscus were collected. Furthermore, additional references were included through searching the references cited by the studies done on the present topic. Related terms were used individually and in combination to ensure a thorough literature search. To stay informed on a topic and incorporate recent knowledge, research articles, books, conference proceedings, and survey reports of relevant public health organizations were selected. Data was collected based on a broader overview for its interpretation in context of present topic. The present review aims to systematically analyze published data on the effects of plant constituents derived from Hibiscus species on cancer. This was achieved by searching databases including SCOPUS, Web of Science and EMBASE, PubMed, Swissport, Google and the Cochrane Library. From this general approach, findings and results were identified and summarized in this final review. This review highlighted antiparasitic activity of plant natural products against helminths and protozoans.

Hibiscus species

Hibiscus Cannabis hydro alcoholic extract, ethanolic extract, and water extract of Hibiscus Cannabis L anti-helminthic activity [1]6. Similarly, ferulic acid isolated from Hibiscus metabolism was found active against on filarial parasite Setaria cervix [17]. Ferulic acid causes an increased proapoptotic gene expression and decreased expression of anti-apoptotic genes simultaneously with an elevated level of ROS and gradual dose dependent decline of parasitic GSH level [17]. Similarly, Hibiscus rosa-sinensis was found highly efficacious against intestinal-helminthic infections. H. rosa-sinensis leaf extract showed antiparasitic efficacy against H. diminutive, a zoonotic tapeworm [18]. It has caused significant reduction in eggs per gram (EPG) of faces and worm counts and result in paralysis of worms at a dose of 40 mg/ml extract [18] (Table 1).

Argemone Mexicana 

Strongyloidiasis is a parasitosis that represents a public health problem, in tropical regions. Argemone Mexicana, extract contains berberine (Ber) that was found active against the third-stage larvae (L3) of Strongyloidiasis Venezuelans in-vitro experiments at a very low dose. It shows anti-hemolytic activity and protects the human erythrocytes from Strongyloidiasis Venezuelans. Similarly, crude extract of A. Mexicana (Am) showing LC50 response values of 1.6, 19.5, and 92.1 μg/mL, at 96 h respectively [19]. The n-hexane fraction contains phytocompounds that cause significant reduction in parasitemia. Similarly, an oral dose of 200 and 400 mg/kg dose Argemone Mexicana extract and fractions for five days showed high antitrypanosomally activity Trypanosoma brucei [20]. A. Mexicana contains saponins, that showed antitrypanosomally activity but absent in fractions that showed no or weak antitrypanosomally activity (Table 1).

Allium species

Garlic Allium sativum was highly effective has been found to be effective against gastrointestinal parasites of humans and animals. Garlic (Allium sativum) contains sulfur-containing compounds such as “Allicin,” “Ajoene,” which showed antileishmanial activity [21]. Dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs were found active against Leishmaniasis [21]. These also were found active against Trypanosoma b. brucei and Leishmania tarantula [22.] Garlic also shows therapeutic effects against Schistosoma mansion experimental infection [23]. Cryptosporidiosis and Toxoplasmosis [24]. It was also found effective against Hymnologists nana and giardiasis [25] and gastrointestinal parasites mainly cestodes and on trematodes [26]. It also shows killing effects in Blastocystis hominis and African trypanosomes [27], and intestinal flagellates of poultry animals [28]. Intake of crushed garlic reduce the worm burden more efficiently than PZQ [29] (Table 1).   

Garlic extract shows tidal activity against protozoans such as Entamoeba histolytica, Hymenoplasties nana, and Giardia lamblia [30]. Ajoene cream found effective against Tinea pedis (athlete’s foot) as 1% terbinafine (Lamisil) cream [31]. Allicin shows inhibitory effect of on the growth of Babesia and T. equi protozoa parasites attack mostly donkeys, horses, and mules [Table 3]. [32]. A. cepa oil is proved highly beneficial in worm infection mainly against cryptosporidium parvum Schistosoma mansoni in experimental mice [23]. The onion is found effective against eelworm (Ditylenchus dipsaci), a tiny parasitic soil living nematode, and cause swollen distorted foliage (Table 1). 

Neem:

Neem Azedarach indica, has much wider use in traditional medicine.   It contains several biologically active constituent azadirachtin, myelination and salami [33]. These constituents are strong anthelminthic in nature. In Indian Ayurveda medicine system neem is an established medicine for treatment of malaria and intestinal parasites that is used since centuries. Similar antimalarial activity of neem plant is mentioned in Ayurveda 2000 B.C. (by Charaka) and 1500 B.C. (by Sushruta). (Azedarach indica) crude neem leaf powder shows anthelmintic efficacy against bovine strongylosis. Its formulations are used in oral dose [34.] Azadirachtin displays both antimicrobial and antifungal properties [35,36]. Neem active ingredients not only protect cattle from helminthic diseases mainly Haemanthus contorts in goats [37].  Thus, it saves quality of meat, milk, and other dairy products (Table 1).    

Curcuma longa

Curcumin [1,7-bis (4-hydroxy-3-methoxyphenyl) -1,6- heptatriene -3, 5-dione] is the major active ingredient of turmeric the Curcuma longa L. This is a polyphenolic compound that is isolated from Curcuma longa rhizome [38]. It exhibits a wide range of pharmacological activities including anti-parasitic effect. It was found active against Benita Benoit [39]. Benita Benoit is the causative agent of bovine bismuthosis. This parasite heavily reduced fertility and productivity in cattle causing high economic losses. It imposes diversity of anasarca, oedema, orchitis, hyperkeratosis, and characteristic skin and mucosal cysts, B. besnoiti tachyzoite and bradyzoite replicate inside intermediate host tissues. It also replicates in primary bovine umbilical vein endothelial cells (BUVEC) in vitro. The natural compound curcumin reduces B. besnoiti tachyzoite viability, by 56% mortality (IC50 5.93 3M) in treatments. Curcumin lowers down viability, motility, invasive capacity, and proliferation of B. Benoit tachyzoites [40]. Curcumin was found highly effective against schistosomiasis mansion in infected mice.  For enhancing the anti-parasitic action turmeric is dissolved in olive oil or in combination with praziquantel (PZQ) in treatment of schistosomiasis mansion infected mice. Turmeric significantly reduced parasite worm burden, granuloma size and consequently the pathology of affected liver, it still far less effective than PZQ [41] (Table 1).    

Aloe vera  

Aloe vera is rich in so natural bio-organics, its major constituent aloe-emodin was found highly effective against helminths Heteractis Gallina rum which infect chickens [42] and Haemanthus contorts from sheep [43]. Aloe vera crude extracts and latex of Aloe pulcherrima showed ant plasmodial activities activity [44].

Cassia sanguine

Cassia sanguine is used against acute malaria attack in North Nigeria [45]. The methanol extract of Cassia alata L. [46] and C. fistula [47] showed ant plasmodial activity Kaushik NK et al, 2015[48]. It kills Plasmodium falciparum Gametocytes [49]. Ethanolic extract of root and stem bark of Cassia Siberian showed ant plasmodial activity in mice model [50]. Hexane extract from the fruits showed significant antileishmanial activity against the promastigote form of Leishmania L. Chagas [51]. Cassia siamea also shows ant plasmodial activity [52] that may be due to the presence of cassiris A and B, novel alkaloids [Table 1][53].

Aegle marvels 

A. marvels extracts showed the anti-filarial effect and are traditionally used to treat Burgi Malaya microfilariae [54,55]. Decoction of A. marvels plant leaves is traditionally used as an anti-malarial agent in the South India [56,57].

Calotropis proceri

Ethanol extracts of C. proceri leaves, stems, roots, flowers and buds showed in vitro schizonticide activity against chloroquine (CQ)-sensitive and CQ-resistant Plasmodium falciparum strains [58]. Similarly, n‑hexane soluble portion of the chloroform extract of root bark of C. gigantea shows in vitro anti‑amoebic activity against the HK-9 strain of Entamoeba histolytica [59]. Compounds isolated from dry leaves of C. proceri found to be active against the malaria parasite [60] while Calotropis gigantea non‑polar fractions were found active against amastigotes of Leishmania major [61]. Similarly, acerogenins isolated from C. proceri latex also showed anti‑plasmodial activity and display inhibitory effect on P. falciparum [62], Leishmania and Trypanosoma species [63]. Similarly solvent extracts of aerial parts of C. proceri showed antimalarial [64], antiproliferative and ant plasmodial activities [65]. Its herbal concoction showed anticoccidial activity in broiler chickens challenged with Eimeria tremella [66] (Table 1). 

Aqueous extract of C. proceri flowers showed very good anthelmintic activity against nematodes in sheep [67] A single oral dose of 0.01 ml or 0.02 ml/kg body weight reduced and obstruct nematode egg production. [68] It also shows anticoccidial activity in sheep (single oral doses of 0.02 ml/kg body weight) mainly in lambs. [69]. The latex of C. proceri also displays acaricidal effect in vitro [70] and also actively work against intestinal worms in children. [71] (Table 1).   

Cleome viscose

Cleome viscose solvent extracts show very high nematocidal activity against plant parasitic nematode Meloidogyne incognita Chitwood. Similar nematocidal activities was observed against root‑knot nematode Meloidogyne avania [72]. Cleome autosperm ethanolic extract showed moderate activity against P. falciparum chloroquine sensitive strain D7 strain in vitro (IC50 value of   54.25 µg/mL). This activity did not find in aqueous extract [73]. Similarly, the diethyl ether fraction was found to be the most potent fraction and showed good ant plasmodial activity (IC50 value of 8.1 µg/mL). However, certain phyto‑constituents like terpenoids or flavonoids have been found to be responsible for anti‑malarial activity [74][75] (Table 1).   

Flavonoid glycoside isolated from C. viscose [76] and C. bur Manni exhibited significant anthelmintic activity [77]. Similar anthelmintic activity is also reported in C. serrulate [78]. The crude alcohol and aqueous extracts of the seeds of C. viscosa Linn. showed anthelmintic activity against Phreesia posthuma and Ascardia galli at a concentration ranging from 10 to 100 mg/mL [77]. Ethanolic leaf extract of fringed spiderflower (Cleome autosperm) showed the anthelmintic potential against the Indian earthworm P. posthuma [79]. Similar anti-helminticactivity is also reported in Cleome viscose seed extracts possess anthelmintic Activity [80] (Table 1). 

Tinospora species

Tinospora crispa leaf extract showed good anti-plasmodial activity [81]. This plant is also found in Indonesia where it is used for the traditional treatment of malaria and Leishmaniasis by local people. It was found highly active against Plasmodium falciparum and also against Babesia diverges and Leishmania infantum. It shows cytotoxicity to sporozoites activity (IC50 values <3> (Table 1).   Similarly, dried stems (ST) of T. crisp and four other plants slowed anti-filarial activity; these have cut down relative movability of adult worms of sub periodic Brugia malayi [87].

Capparis spinosa

Capparis spinosa (EtOAc fraction) showed pronounced antiprotozoal activity against P. falciparum with an IC50 0.50 microg/mL in MRC-5 cell line (CC (50) > 30 microg/mL). Heliotropism curassavicum (CHCl(3) fraction) showed similar activity against P. falciparum (IC50 0.65 microg/mL; MRC-5 CC(50) > 30 microg/mL).  [88] C. spinosa contain lectins, which control Leishmania major promastigotes by agglutination inside its vector host, Phlebotomus papayas in laboratory assays. Capparis spinosa lectins do fast agglutination and kill the parasites. High mortality of promastigotes was occurred in infected flies after they ingested an extract of C. spinosa with the diet. The results indicate that the lectins found in the vegetation in L. major foci may decrease the transmission of the parasite [89] (Table 1). Capparis spinosa is also used to control Leishmania major infection [59]. Capparis spinosa contains cad bicine an alkaloid, betasitosterylglucoside-6’-octadecanoate (1) and 3-methyl2-butenyl-beta-glucoside, which showed anti-parasitic activity [90]. The root extract of C decidua is shown to have purgative activity, while root bark and pulp are used to kill helminths. Similarly, Capparis spinosa fruit diet cut down alpha-amylase and alpha-glucosidase activities both inside Phlebotomus papatasi gut and in salivary gland preparations. Due to inhibition of these two enzymes C decidua extract shows the ability to control Leishmania major and L. infantum, L. donovani, L. braziliensis, Cerithiid fasciculata and Hepatomas muscarum parasites [91]. Plant caused significant mortality in above parasite [91] (Table 1). 

Conclusion:

Plants possess diverse bioorganic compounds with a wide range of pharmacological activities, including antiparasitic activity. In addition to the above ingredients, plant latex, gums and alkaloids, terpenes, ferulic acid and other natural products also showed antiparasitic effects. Most of these components have been tested in in vitro cultures. Therefore, they need to be tested in appropriate in vivo animal models to determine pharmacokinetics, bioavailability, and pharmacodynamics. Nevertheless, the low cost and convenience of producing herbal antiparasitic preparations make them cost-effective medicines and drugs for ensuring the safety of cattle and other livestock around the world, especially in Africa, South America, and Asia.  AIt has become. In addition, preventive, hygienic and good hygiene measures should be taken to combat infections caused by parasites.Take precautions; keep children away from garbage, contaminated soil, dirty water, and areas with bad odors. Always wash vegetables with salt water to kill eggs and parasite larvae, eat properly cooked meat, and drink purified drinking water.

Acknowledgements: 

The authors are thankful to HOD Zoology for facilities.

 

Conflicts of Interest

The author declares no conflicts of interest regarding the publication of this paper.

Hemerythrin and Chloroxylon Ine isolated from Todd Alia asiatica were found active against parasitic ciliate Ichthyophthirius multifils [92]. Both bio-organic constituent’s chelerythrine and chloroxylonine were found 100

References

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad