**2. Therapeutic approaches and their limitations**

Leishmaniasis is one of the most common NTDs, and it comes with a slew of negative and life-threatening consequences, including significant morbidity, early death, and long-term disability. Treatment entails limiting illness spread and utilizing existing criteria, but present medicines, such as chemical pharmaceuticals, need long-term treatment, minimal efficacy, and a slew of hazardous side effects. Only a few prevention strategies are available, despite the fact that no appropriate medications have been produced to prevent the virus, which is widely transmitted among the human population [12]. Some clinically approved medications are discovered among them to treat this endemic condition, that is, meglumine antimoniate (glucatime), sodium stibogluconate (pentostan), amphotericin B, and miltefosine. Excessive use of these chemotherapeutic sources, on the other hand, has been linked to antagonistic consequences [13]. As a result, researchers are looking for natural ways to treat leishmaniasis. Leishmaniasis treatment using chemical-based drugs various pharmacological medications, such as amphotericin B, pentamidine, miltefosine, and paromomycin, have been used in the treatment of leishmaniasis for numerous years. Due to the time-consuming method and high toxicity paired with significant adverse effects, none of the clinically approved medications could be considered as the ultimate source of treatment. Furthermore, the most commonly used medications do not completely eliminate parasites from all afflicted individuals [14]. The applications of several of these drugs, as well as their drawbacks, are explained further below. Pentavalent antimonials can be given via intravenous, intramuscular, and intralymphatic methods, with an optimum dose of 20 mg/kg/day (28–30 days) and a potentiality of 35–95%. This medicine can cause toxicity such as nephrotoxicity, hepatotoxicity, severe cardiotoxicity, and pancreatitis if used excessively [12, 13]. Miltefosine, when given orally, had an inhibitory effect on *Leishmania* growth but also had a negative effect, causing severe infection symptoms such as nephrotoxicity, teratogenicity, vomiting and diarrhea, and hepatotoxicity [15]. Paromomycin, which is also used to treat leishmaniasis, has been documented to have several hazardous side effects during treatment, including severe nephrotoxicity, hepatotoxicity, and ototoxicity [16]. Pentamidine, at a starting dose of 3 mg/kg/day, has the potential to slow *Leishmania* development while also causing significant side effects including as hypotension, hyperglycemia, tachycardia, pancreatic damage, and electrocardiographic abnormalities changes [14]. Existing chemotherapies have a number of drawbacks, including high cost, increased toxicity, and acquired resistance to parasitic strains, as well as other side

effects during their prevention mechanism, prompting scientists and medical practitioners to develop a new therapeutic system to treat NTDs. Plant extracts, bioactive chemicals, and secondary metabolites obtained from specific plant species, as well as various types of NPs manufactured using plant extract, have become promising as well as safer preventative medicines in recent decades.
