Human placental extract offers protection against experimental visceral leishmaniasis: a pilot study for a phase-I clinical trial

Abstract

An aqueous extract of human placenta (HPE) was found to offer protection against established experimental visceral leishmaniasis in BALB/c mice and hamsters, whether the Leishmania donovani strain involved was one that was sensitive or resistant to pentavalent antimony. Intraperitoneal administration of the extract, into mice or hamsters that had been infected 2 months previously, led to antileishmanial T-cell proliferation among splenic mononuclear cells, the generation of host-protective cytokines (interferon-gamma, tumour necrosis factor and interleukin-12) and the upregulation of the expression of inducible nitric oxide synthase (and subsequent NO generation) in splenocytes. Furthermore, splenic macrophages from the HPE-treated mice showed increased generation of reactive oxygen species and enhanced surface expression of antigens of major histocompatibility complex class II (MHCII), and the extract restored the otherwise-defective antigen-presenting ability of the macrophages. Thus, in mice and hamsters infected with L. donovani, HPE therapy can stimulate both arms of the host's immune system and favour the complete resolution of the leishmanial infection. Among five human cases of visceral leishmaniasis, 30 daily intramuscular injections of HPE, at doses much lower than those used in the experimental infections, also gave very promising results. Based on the results of this pilot study, a further evaluation of the efficacy of HPE therapy, which may offer a cost-effective way of improving the treatment of antimony-resistant cases of visceral leishmaniasis, is being undertaken.

Aqueous Extract of Human Placenta

“…It has been reported that an aqueous extract of human placenta was found to offer protection against established experimental visceral leishmaniasis in BALB/c mice and hamsters, whether the Leishmania donovani strain involved was one that was sensitive or resistant to pentavalent antimony. Based on the results of this pilot study, a further evaluation of the efficacy of human placental extract therapy, which may offer a cost-effective way of improving the treatment of antimony-resistant cases of visceral leishmaniasis, is being undertaken (Chakraborty et al, 2008).…”

Immunomodulation by chemotherapeutic agents against Leishmaniasis

“…Interestingly, Cystatin along with IFN-γ, induced generation of NO but markedly reduced expression of iNOS at both mRNA and protein levels [49][50][51]. Other compounds that showed similar NO enhancing activity were Artemisinin [22], quassin [19], an aqueous extract of human placenta [52], eugenol-rich essential oil from Ocimum gratissimum [53], glycolipids along with other constituents from Desmodium gangeticum [54], a linalool-rich essential Oil from Croton cajucara [55], Kalanchoe pinnata [56,57] and Aloe vera leaf exudate [58,59]. A similar observation was evident following treatment with Chenopodium ambrosioides essential oils [60], Pyrazinamide [61], Himathantus sucuuba Latex (HsL) [62], quinovic acid glycosides and cadambine acid [63].…”

“…Miltefosine [41,42,74], glucantime [79], and Amphotericin B [43] along with experimentally effective compounds such as 18 Beta-glycyrrhetinic acid [46], tannins [47,80,81], artemisinin [22], quassin [19], aqueous extract of human placenta [52], garlic [82], pyrazinamide [61], CpGcontaining oligodeoxynucleotide [64], Berberine chloride [66] and 2,3,7,8-Tetrachlorodibenzo-P-dioxin [65], collectively support the notion that upregulation of the Th1 response is an effective strategy for parasite elimination. IL-6 and IL-1β are potent pro-inflammatory cytokines involved in the generation of NO and macrophage activation which are increased by antimonials [83], tannins and related compounds [47,80,81] as also sage phenolics [84].…”

“…The impaired expression of CD86 on monocytes as evidenced in PKDL was markedly increased following treatment with Miltefosine and SAG, the effect of Miltefosine being greater [92]. Pyrazinamide enhanced expression of CD80 and CD86 in Leishmania infected BALB/C mice [61] as did an aqueous extract of human placenta, evidenced by an increased expression of MHC molecules on APCs ( [52], Table 2). …”

Visceral Leishmaniasis: Advances in Treatment

“…Patents with demonstrated antileishmanial activity include the coral reef sea cucumber Actinopyga lecanora, herbal extracts from Aloe vera leaf and night jasmine leaf Nyctanthes arbortristis tested in mice and hamster models, respectively, and a human placental extract with demonstrated activity in humans with VL in India [70][71][72][73]. Allicin, a compound found in garlic, has also antileishmanial activity.…”