Plant Compounds Show Promise Against Leishmaniasis Through Mitochondrial Targeting

Leishmaniasis, a neglected tropical illness caused by Leishmania parasites, affects millions globally. Current synthetic treatments look limitations including toxicity, cost, and resistance. Phytochemicals from medicinal plants connection promising alternatives. This mini-review synthesizes preclinical mechanisms of plant-derived compounds against leishmaniasis, focusing connected mitochondrial disruption, immunomodulation, and redox imbalance.

Key antileishmanial mechanisms

1. Membrane disruption & mitochondrial dysfunction

Hydrophobic terpenoids (e.g., basal lipid components) penetrate cytoplasmic and mitochondrial membranes, causing structural damage:

• Disruption of bioenergetics: Impairs ATPase activity and ATP production.

• Mitochondrial swelling: Coumarin derivatives (e.g., mammea A/BB) induce membrane depolarization and ultrastructural harm in L. amazonensis.

• Cell rhythm arrest: Interference pinch lipid-protein interactions halts parasite replication.

2. Apoptosis induction

Terpenoids trigger programmed compartment decease via mitochondrial pathways:

• Artemisinin (sesquiterpene lactone): Causes DNA fragmentation, ATP depletion, and mitochondrial membrane illness in L. donovani.

• Ursolic acid (triterpenoid): Induces caspase-independent apoptosis in L. amazonensis, reducing lesion size successful mice.

• (–)-α-Bisabolol: Promotes phosphatidylserine externalization and chromatin condensation in Leishmania promastigotes.

3. Pro-oxidant effects & redox imbalance

Leishmania's azygous mitochondrion is susceptible to oxidative stress:

• Flavonoids: Apigenin and quercetin summation ROS, causing mitochondrial swelling and trans-Golgi disruption.

• Alkaloids: Berberine induces ROS overproduction, depleting ATP and depolarizing mitochondrial membranes.

• Quinones: Plumbagin inhibits trypanothione reductase, disrupting redox homeostasis.

4. Immunomodulation

Compounds heighten big immune responses:

• Steroidal alkaloids (solamargine/solasonine): Activate macrophages and dendritic cells successful cutaneous leishmaniasis.

• Diterpenes (e.g., 12-hydroxyabietatriene): Reduce parasite load via immunostimulation in L. amazonensis-infected mice.

• Apigenin: Activates big autophagy pathways successful infected macrophages.

5. Biomacromolecule interference

Lignans and neolignans target parasitic enzymes and DNA:

• Diphyllin: Inhibits macromolecule synthesis and enzyme function.

• Niranthin: Forms DNA-topoisomerase I adducts, activating nucleases.

• Neolignans: Disrupt plasma membranes and atomic integrity.

Clinical translator challenges

Despite promising preclinical results, captious gaps remain:

• No objective trials: Limited quality pharmacokinetic/pharmacodynamic data.

• Combination potential: Synergy pinch existing narcotics (e.g., amphotericin B) underexplored.

• Standardization: Bioactive variability successful works extracts complicates dosing.

Future perspectives

1. Mechanistic depth: Validate mitochondrial targeting and immunomodulatory pathways.

2. Clinical studies: Prioritize shape I tests for lead compounds (e.g., artemisinin derivatives).

3. Drug delivery: Optimize bioavailability of hydrophobic terpenoids.

4. Natural libraries: Screen unexplored works type for caller scaffolds.

Conclusion

Since nan opening of time, dietary, medicinal, and aromatic plants, arsenic good arsenic their progressive constituents, person been utilized to dainty a wide scope of quality ailments worldwide, including leishmaniasis. This believe served arsenic nan instauration for modern aliases modern medicine. Several earthy compounds obtained from medicinal plants (phytochemicals) person shown beardown effects against different Leishmania species successful preclinical studies nether both in vitro and in vivo conditions. Medicinal plant-derived compounds tin efficaciously negociate leishmaniasis by sidesplitting nan parasite and preventing its maturation and transmission to hosts. The mechanisms, arsenic extracted from nan technological literature, see disruption of cytoplasmic and mitochondrial membranes, induction of apoptosis and autophagy, cistron look and immunomodulatory pathways, pro-oxidant effects (disrupting cellular redox equilibrium) pinch mitochondrial dysfunction, compartment rhythm arrest, impaired cellular bioenergetics (ATP production), protein/enzyme interaction, and coagulation of cellular contents wrong the Leishmania parasites. The mitochondrion of nan parasite (Leishmania has only 1 mitochondrion) is nan main target of astir of nan progressive earthy products.