Natural Products: Insights into Leishmaniasis Inflammatory Response

Table 1

Plant extracts and isolated compounds with antileishmanial and immunomodulatory activities.

Plant species	Substance or extract	In vitro activity (IC50)	In vivo in mice	Substance cytokines activity	Reference
Glycyrrhiza glabra L.	18-glycyrrhetinic acid	L. donovani; 4.6 μg/mL	L. donovani; 50 mg/kg/day	Reduces levels of IL-10 and IL-4, but increases levels of IL-12, IFN-, TNF-, and inducible NO synthase	[57]
Tanacetum parthenium	Parthenolide	L. amazonensis; 0.37 μg/mL	—	Inhibits IB kinase	[58]
Baccharis uncinella	Oleanolic acid and ursolic acid	—	L. amazonensis; 1 and 5 mg/kg/day	Increases IL-12 and IFN- cytokines	[51, 59]
Dictyota pfaffii	Dolabelladienetriol	L. amazonensis; 43.9 μM	—	Diminishes TNF- and TGF- production in uninfected and Leishmania-infected macrophages	[60]
Artemisia indica	Artemisinin	L. donovani, L. infantum, L. tropica, L. braziliensis, L. mexicana, and L. amazonensis; 100 μM to 120 μM	L. donovani; 10 mg/kg and 25 mg/kg body weight	Restores Th1 cytokines (interferon-gamma and interleukin-2)	[61]
Glycyrrhiza glabra	Glycyrrhizic acid	—	L. donovani; 1, 10, 25, 50, 75, or 100 mg/kg body weight/day	Enhances the expression of IL-12 and TNF-, in parallel with a downregulation of IL-10 and TGF-	[37]
Nectandra leucantha	(a) Dehydrodieugenol B,; (b) 1-(8-propenyl)-3-[3′-methoxy-1′-(8-propenyl)phenoxy]-4,5-dimethoxybenzene, and; (c) 1-(7R-hydroxy-8-propenyl)-3-[3′-methoxy-1′-(8′-propenyl)-phenoxy]-4-hydroxy-5-methoxybenzene	(a) 26.7 μM (L. donovani),; (b) 17.8 μM (L. donovani), and; (c) 101.9 μM (L. donovani)	—	((a) to (c)) Reduced production of IL-6 and IL-10.; Minimal effect on nitric oxide production in L. donovani-infected macrophages	[56]
Quassia amara	Quassin	—	—	Upregulating proinflammatory cytokines such as TNF- and IL-12	[62]
Vitis vinifera	Resveratrol	L. amazonensis; Antipromastigote activity (27 ± 0.59 μM); Antiamastigote activity (42 ± 7.18 μM)	—	Decreases the levels of the proinflammatory cytokine TNF- in infected macrophages stimulated with IFN-	[63]
Raputia heptaphylla	11,19-dihydroxy-7-acetoxy-7- deoxoichangin	L. (V) panamensis J774.2 EC50 = 7.9 μM; hDCs EC50 = 25.5 μM	—	Increases on the production of IL-12p70, TNF-, and NO, as also, in the number of hDCs HLA-DR-positive in treated infected hDCs	[64]
Galipea longiflora	Crude extract containing 13 different quinolinic alkaloids and 2-phenylquinoline as major compounds	L. braziliensis; IC90 = 20 μg/mL	L. braziliensis; 6.25 and 12.5 mg/kg/day	Reduced production of IFN-, IL-12, and; TNF- by spleen cells.; Reduced the inflammatory reaction in mice infected with L. braziliensis promastigotes	[40, 41]
Xylopia discreta	(a) Methanol extracts containing ~50% of alkaloids and terpenes (-pyrenes, camphene, -myrcene, and 1,8 cineol) and (b) essential oil	(a) L. panamensis in J774; LC50 = 598.37 μg/mL and EC50 = 9.32 μg/mL,; (b) L. panamensis in J774; LC50 = 857.7 μg/mL and EC50 = 37.5 μg/mL,; (a) L. panamensis in U937; LC50 = 698,45 μg/mL and EC50 = 6,35 μg/mL,; (b) L. panamensis in U937; LC50 = 160 μg/mL and EC50 = 6.25 μg/mL	—	Increased the secretion of MCP-1 by U937 and J774 cell lines	[42]
Galium mexicanum	Hexane fraction (HE 5)	L. donovani; MIC = 333 μg/mL	—	Reduced production of IL-6 in THP-1 cells	[49]
Laennecia confusa	(a) Aqueous extract and chloroform extracts (antileishmanicidal),; (b) methanol, and (c) chloroform extracts (anti-inflammatory)	L. donovani; (a) IC50 = 20 μg/mL and; IC50 = 20 μg/mL	—	(b) Reduced IL-6 production in THP-1 cells	[48]
Azadirachta indica	Ethyl acetate extract fraction	L. donovani; IC50 = 52.4 μg/mL	L. donovani; 100 mg/kg body weight	Increased the expression of TNF-, IL-8, and IL-1 in THP-1 cells and TNF-, IFN- in PBMCs	[46]
Azadirachta indica	Leaves ethanol extract (ALE) and seeds ethanol extract (ASE)	Antipromastigote; IC50 = 34 and 77,66 μg/mL (ALE and ASE).; Antiamastigote; IC50 = 17,66 and 24,66 μg/mL (ALE and ASE)	—	Increased the expression of INF-, TNF-, and IL-2 and declined in IL-4 and IL-10 levels in spleen cells	[47]
Lopezia racemosa	Hexane extract fractions (HE11–14b)	IC50 = 30,66 μg/mL	—	Reduced IL-6 production in THP-1 cells	[50]
Croton caudatus	Semipurified hexane extract (JDHex)	L. donovani; Antipromastigote; IC50 = 10 μg/mL.; Antiamastigote; IC50 = 2.5 μg/mL	L. donovani; 1.25, 2.5, 3.75 or 5 mg/kg body weight for five days	Increased the production of IL-12 and TNF- in murine peritoneal macrophages in vitro.; Increased the intracellular IFN- and decreased the IL-10 production in CD4^+ T cells in vivo	[39]
Baccharis uncinella	Triterpenic purified fraction containing oleanolic and ursolic acids	—	L. amazonensis; 1.0 mg/kg and 5.0 mg/kg for five days	Increased the IL-12 and IFN- production in mice	[51]
Sambucus nigra	Commercial preparation (Sambucol)	—	L. major; 25 μL twice a day	Increased the production of IL-1, IL-6, IL-8, and TNF- by human monocytes	[65]
Syzygium cumini	Essential oil (ScEO) containing as major component -pinene	L. amazonensis; Antipromastigote; IC50 = 19.7 μg/mL	—	Increased in lysosomal volume, phagocytosis, and NO production by peritoneal macrophages	[66]
Artemisia annua	Hexane extract	—	L. donovani; 50, 100 and 200 mg/kg body weight daily for ten days	Increased in levels of IFN- and reduction of levels of IL-4 and IL-10 in serum and culture supernatant of lymphocytes from mice	[53]
Piper nigrum	Alkaloids (piperine and analogue phenylamide)	L. amazonensis; Antipromastigote; IC50 = 14.2 μM.; Antiamastigote; IC50 = 28 μM	—	Suppressed MCP-1, TNF-, NF-KB activation, and NO production in vitro and in vivo and showed anti-inflammatory properties	[55, 67]
Tinospora cordifolia	Pure herb extract (tablet form)	—	Leishmania donovani; 100 mg/kg b.wt. for 15 days daily	Enhanced proliferation and differentiation of lymphocytes and induced Th1 immune response and IFN- and IL-2, but declined IL-4 and IL-2 levels	[68]
Withania somnifera	Aqueous extract	—	L. donovani; 5 mg/kg/day	Increased antileishmanial efficacy of cisplatin.; Increased in the levels of IFN- and IL-2 (Th1-type immunity) and the levels of IgG2 over IgG1.; Decreased in levels of IL-4 and IL-10	[69]
Lophanthera lactescens	6,7,15,16,24-pentacetoxy-22-carbomethoxy-21, 22-epoxy-18−hydroxy-27,30-bisnor-3,4-secofriedela-1,20 (29)-dien-3,4 R-olide (LLD-3)	L. amazonensis .; Antiamastigote; IC50 = 0.41 μg/mL	—	Affected proliferation of naïve or activated B and T cells, as well as the B cells immunoglobulin synthesis	[54]