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The use of medicinal plants in the treatment of malaria is gaining global attention due to their efficacy and cost effectiveness. This study evaluated the bioactivity-guided antiplasmodial efficacy and immunomodulatory effects of solvent fractions of Diospyros mespiliformis in mice infected with a susceptible strain of Plasmodium berghei (NK 65). The crude methanol extract of the stem of D. mespiliformis (DM) was partitioned between n -hexane, dichloromethane, ethyl acetate and methanol. Male Swiss mice (20 ± 2 g) infected with P. berghei were grouped and treated with vehicle (10 mL/kg, control), Artemether lumefantrine (10 mg/kg), 100, 200 and 400 mg/kg of n -hexane, dichloromethane, ethyl acetate and methanol fractions of D. mespiliformis for seven days. Blood was obtained for heme and hemozoin contents while serum was obtained for inflammatory cytokines and immunoglobulins G and M assessments. Liver mitochondria were isolated for mitochondrial permeability transition (mPT), mitochondrial F 1 F 0 ATPase (mATPase) and lipid peroxidation (mLPO) assays. The GC–MS was used to identify the compounds present in the most potent fraction. The dichloromethane fraction had the highest parasite clearance and improved hematological indices relative to the drug control. The heme values increased, while the hemozoin content significantly ( P  < 0.05) decreased compared with the drug control. The highest dose of HF and MF opened the mPT pore while the reversal effects of DF on mPT, mATPase and mLPO were dose-dependent. The levels of IgG, IgM and TNFα in the DF group were significantly higher than the drug control, while the IL-1 β and IL-6 values did not vary linearly with the dose. Lupeol and Stigmastan-3,5-diene were the most abundant phytochemicals in the DF. The outcome of this study showed that the DF has immunomodulatory effects in infected mice, reduced proliferation of the malaria parasite and thus protect liver cells.

Small interfering RNA (siRNA) has been deemed a promising therapeutic method for treating diverse diseases. siRNA-based therapeutics provide a distinct mechanism of action by selectively targeting and silencing disease-causing genes at the post-transcriptional level. This paper provides an overview of the present state of siRNA-based therapeutics, highlighting their potential in different therapeutic areas. The first section of this review introduces the basic principles of siRNA technology, including its mechanism of action and delivery methods. Subsequently, we discuss the impediments associated with siRNA delivery and manufacturing development and the strategies for overcoming these obstacles. The clinical advancement of siRNA therapeutics in various disease areas, including cancer, genetic disorders, viral infections, and inflammatory diseases, is summarized. Lastly, we summarize the successes, failures, and lessons learned from the development of siRNAs. With advancements in delivery systems and improvements in target selection, the field of medicine can be revolutionized, and siRNA therapeutics can offer new treatment options for patients.

Plasmodium infection causes inflammation in the host. A combination of herbs like Azadirachta indica and Curcuma longa may have beneficial effect in remediating inflammation in malaria disease. The aim of this study is to investigate the immunomodulatory and synergistic effects of the association of Azadirachta indica and Curcuma longa in experimental Plasmodium berghei infection. Fifty male Swiss mice were infected with chloroquine susceptible (NK 65) strain of Plasmodium berghei intraperitoneally. Parasitemia was confirmed using microscopy and the animals were grouped ( n  = 5), treated once daily and orally for 7 days with 200 and 400 mg/kg of A. indica and C. longa methanol extracts. Four hundred milligrams per kilogram A. indica was combined with the two doses of C. longa methanol extract and fractions. Negative control was treated with 10 mL/kg 5% (v/v) dimethyl sulfoxide (DMSO, vehicle) while positive control was treated with artemether–lumefantrine (10 mg/kg) and normal control not infected with parasites was treated with distilled water only. Animals were sacrificed on day 7, and blood serum was obtained. Serum immunoglobulins G (IgG) and immunoglobulin M (IgM), C-reactive protein (CRP), tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were assayed using ELISA techniques. Combination of A. indica and C. longa significantly increased ( P  < 0.05) IgG and TNF-α than separate treatment while IgM increased albeit insignificantly ( P  < 0.05); CRP and IL-1β decreased significantly relative to control ( P  < 0.05) while IL-6 levels was modulated both in separate and combined therapy. Separate administration and combinations of A. indica and C. longa have immunomodulatory effects in malaria-infected mice.

Complete malarial therapy depends largely on the immunological and inflammatory response of the host to the invading potentials of malarial parasite. In this study, we evaluated the roles of betulinic acid on immunological response, anti-inflammatory potentials, cardiac and skeletal muscle tissue damage in mice infected with chloroquine susceptible (NK 65) and resistant (ANKA) strains of Plasmodium berghei . Serum Interleukins 1β and 6 (IL-1β, IL-6), tumour necrosis factor alpha (TNF-α), immunoglobulins G and M (IgG and IgM), C-reactive protein (CRP) and creatine kinase (CK) were determined using ELISA technique. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutammyl transferase (GGT) were determined using ELISA technique. The results showed that betulinic acid decreased the levels of IL-1β, IL-6, TNF-α and CRP relative to the infected control. The IgG and IgM levels significantly increased in both models while CK did not decrease significantly in both models although serum AST, ALT and GGT significantly decreased compared to the infected control. These results showed that betulinic acid possessed anti-inflammatory, immunomodulatory and remediating effects on tissue damage. Furthermore, the decrease in activity of CK brought about by betulinic acid is indicative of decrease in cardiac and skeletal muscle injury which is a major pathological concern in Plasmodium infection and treatment.

Introduction: Unmanaged Diabetes Mellitus (DM) usually results to tissue wastage because of mitochondrial dysfunction. Adverse effects of some drugs used in the management of DM necessitates the search for alternative therapy from plant origin with less or no side effects. Ocimum gratissimum (L.) (OG) has been folklorically used in the management of DM. However, the mechanism used by this plant is not fully understood. This study was designed to investigate the effects of chloroform fraction of OG leaf (CFOG) in the reversal of tissue wastage in DM via inhibition of mitochondrial-mediated cell death in streptozotocin (STZ)-induced diabetic male Wistar rats. Methods: Air-dried OG leaves were extracted with methanol and partitioned successively between n -hexane, chloroform, ethylacetate and methanol to obtain their fractions while CFOG was further used because of its activity. Diabetes was induced in fifteen male Wistar rats, previously fed with high fat diet (28 days), via a single intraperitoneal administration of STZ (35 mg/kg). Diabetes was confirmed after 72 h. Another five fed rats were used as the normal control, treated with corn oil (group 1). The diabetic animals were grouped (n = 5) and treated for 28 days as follows: group 2 (diabetic control: DC) received corn oil (10 mL/kg), groups 3 and 4 were administered 400 mg/kg CFOG and 5 mg/kg glibenclamide, respectively. Body weight and Fasting Blood Glucose (FBG) were determined while Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and beta cell (HOMA-β), and pancreatic tissue regenerating potential by CFOG were assessed. Activity-guided purification and characterization of the most active principle in CFOG was done using chromatographic and NMR techniques. The animals were sacrificed after 28 days, blood samples were collected and serum was obtained. Liver mitochondria were isolated and mitochondrial permeability transition (mPT) was investigated by spectrophotometry. Results: CFOG reversed diabetic-induced mPT pore opening, inhibited ATPase activity and lipid peroxidation. CFOG reduced HOMA-IR but enhanced HOMA-β and caused regeneration of pancreatic cells relative to DC. Lupanol was a major metabolite of CFOG. Discussion: Normoglycemic effect of CFOG, coupled with reversal of mPT, reduced HOMA-IR and improved HOMA-β showed the probable antidiabetic mechanism and tissue regenerating potentials of OG.

Polycystic ovary syndrome (PCOS) is a gynecological disorder among reproductive-aged women and a major cause of infertility. Different treatment options are being employed but with side effects. This has mandated alternative treatment options, especially complementary therapy. This study therefore investigated the possible protective effects of methanol extract of Drymaria cordata in Letrozole-induced PCOS. The plant is folklorically used in the treatment of diverse ailments including PCOS, fibroids, uterine/ovarian/breast tumors, and cancers. Forty-eight female Wistar rats were acclimatized and initially divided into two groups: group I(control group) and group II(PCOS group). PCOS was induced by the oral administration of letrozole/high-fat diet for 21 days. After the induction, the PCOS group was sub-divided into four groups ( n  = 4): group II (positive control with PCOS), group III (MET 2mg/kg), group IV (MEDC 200mg/kg), and group V (MEDC 400mg/kg). Rats were orally treated with MET and MEDC for six weeks after the PCOS induction. At the end of the experimental period, blood samples were collected, sera were separated, mitochondria were isolated, and the mPT, some apoptotic biomarkers, hormonal and lipid profiles, and oxidative stress markers were determined. Ovarian histological evaluation and GC–MS analysis of MEDC were carried out. There was no significant mPT pore opening in the PCOS (untreated) group. However, treatments with MEDC caused significant mPT pore opening, upraised caspase 9, caspase 3, and Bax, and decreased anti-apoptotic Bcl-2 levels. The MEDC treatments restored the hormonal and lipid profiles, increased the levels of GSH-Px and SOD and decreased TBARS. Histological examination revealed resolved ovarian cysts and improved follicular growth with MEDC treatments. Comparable results were observed for both MEDC and metformin. The GC–MS analysis revealed the presence of some major pharmacologically relevant compounds. These findings suggest that MEDC contains phytochemicals that can protect against letrozole-induced PCOS possibly by normalizing the impaired hormonal balance, restoring the lipid profile, and improving the antioxidant milieu of the system. Graphical Abstract

Some antimalarial drugs are immune-modulators that impact multiple pathways of innate immunity in malarial treatment. However, information on the immunomodulatory effects of artequine and rutin in the treatment of malaria remains elusive. Twenty-five Swiss mice (18 ± 2 g) were used for this study. Twenty were infected with Plasmodium berghei (NK65). Parasitemia was confirmed, and the animals were grouped (n = 5) as follows: Group A was not infected but treated orally with vehicle. Groups B to E were infected and treated (B) orally with vehicle (10 ml/kg), (C) with 10 mg/ kg artequine, (D) with 10 mg/kg of artequine supplemented with 100 mg rutin/kg, and (D) with 10 mg/kg of artequine supplemented with 200 mg rutin/kg, for 7 days. Blood was collected for hematological, inflammatory cytokines, and immunoglobulins G and M assays. Post mitochondrial supernatant fraction was used for antioxidant assays. Rutin co-administration (200 mg/kg) significantly (P < 0.001) increased platelet and neutrophil counts (P < 0.01) but significantly (P < 0.01) decreased white blood cell count and lymphocyte relative to parasitized control. Also, it significantly (P < 0.05) decreased lipid peroxidation, xanthine oxidase, and superoxide dismutase activities but significantly (P < 0.05) increased reduced glutathione and glutathione S-transferase activity. Rutin co-administration also caused a significant (P < 0.001) increase in tumor necrosis factor-alpha, interleukin-6, and immunoglobulin M levels, while interleukin-1β and immunoglobulin G decreased significantly (P < 0.001) compared with parasitized control. These results showed that rutin co-administration with artequine improved host antioxidant status and modulated the immune and inflammatory responses.

Background Trema orientalis (T. orientalis Linn) has been used in the management of malaria in the western part of Nigeria and despite its application in ethnomedicine, there is dearth of scientific evidence to justify the acclaimed prophylactic antimalarial usage of the plant. The aim of this study is to assess the in vitro antiplasmodial cell-free assay and chemopreventive efficacy of the methanol extract of the stem bark of T. orientalis and its fractions as a prophylactic regimen for malaria prevention. Also, the antimicrobial activities of the extract and the fractions were investigated. Method Vacuum liquid chromatography was used to obtain dichloromethane, ethylacetate and methanol fractions from the methanol extract of T. orientalis. The fractions were tested for their prophylactic and cell-free antimalarial activity using murine models and β-hematin formation assay respectively. Disc diffusion method was used to determine the antibacterial activity of the extract and its fractions against both Gram-positive and Gram-negative bacteria. Results In the prophylactic experiment, dichloromethane (DCMF), methanol fraction (MF) and extract (ME) (in this order) showed significant chemopreventive effects against P. berghei invasion of the red blood cells when compared with both Sulfadoxine-Pyrimethamine (SP) and untreated controls. Results of the in vitro study showed that the DCMF had the highest effect in preventing the formation of β-hematin when compared with other fractions. The DCMF also had the highest percentage inhibition of β-hematin formation when compared with chloroquine. The extract and fractions showed a concentration dependent antibacterial activity. Methanol extract had a pronounced inhibitory effect on Enterobacter cloaca ATCC 13047 and Enterococcus faecalis ATCC 29212. Serratia mercescens ATCC 9986 and Pseudomonas aeruginosa ATCC 19582 were the most susceptible bacteria. Conclusion The results obtained showed that both extract and fractions of T. orientalis possessed antiplasmodial and antimicrobial activity.

Azadirachta indica A. Juss (Meliaceae) (AI) and Curcuma longa L. (Zingiberaceae) (CL) are used for malaria treatment but their anti-glycolytic and host mitochondrial effects have not been studied. The AI stem-bark and CL rhizomes were extracted with methanol. Methanol extract of CL (Turmeric) was partitioned to yield methanol fraction (MF). Swiss mice infected with Plasmodium berghei (NK 65 strain) were treated with 200 and 400 mg/kg of AI and turmeric for seven days. Turmeric and MF (200 and 400 mg/kg) were combined with 400 mg/kg AI to treat mice infected with Plasmodium berghe i (ANKA strain) for four days. Drug and infected controls mice were treated with artemether lumefantrine (10 mg/kg) and distilled water (10 mL/kg), respectively. Serum lactate dehydrogenase (LDH) and aldolase activities were determined. Liver mitochondria were obtained for mitochondrial permeability transition (mPT) pore opening and F o F 1 ATPase assays. The curcumin content of turmeric was determined using HPLC while LD 50 of Turmeric and AI was also determined. The AI, and its combination with turmeric decreased parasite load and increased chemosuppression in both sensitive and resistant studies while MF and its combinations with AI induced mPT pore opening. In the resistant experiment, AI + Turmeric 400 mg/kg decreased F o F 1 ATPase, LDH and aldolase activities against the infected control. The LD 50 values of both extracts were above 2000 mg/kg while the MF had the highest curcumin content. Antiplasmodial mechanisms of action of AI, CL and their combinations involve anti-glycolytic effects. Their composite formulations are more potent in malaria treatment.

Ficus mucoso is traditionally used to treat bronchial infections. This study compared the efficacy of terpene-rich fractions of F. mucoso root bark on lipopolysaccharide(LPS)-induced inflammation, liver mitochondrial permeability transition (mPT), an index of mitochondrial health, and associated pathological alterations. Terpene-Rich Fractions of Dichloromethane (TRDF) and Ethylacetate Fractions of F. mucoso (TREF) were obtained according to standard procedures. To induce systemic inflammation, a single intraperitoneal injection of 1mgLPS/kgbw was given to mice. Spectrophotometric techniques were used to evaluate the effects of the oral administration of TRDF and TREF (3 days) on levels of pro-inflammatory mediators (TNF-α, IL-1β, IL-6) using ELSA techniques as well as antioxidant indices in normal and LPS-treated mice. The mPT pore opening, mitochondrial ATPase activity and lipid peroxidation were monitored spectrophotometrically. Our results revealed that treatment with LPS caused significant elevation in serum cytokine levels while administration of 50 and 100 mg/kg TRDF and TREF significantly reduced elevated serum levels of cytokines (TNF-α, IL-1β, IL-6) in LPS-challenged mice. In addition, activitities of superoxide dismutase, catalase and liver marker enzymes (ALT and AST) as well as levels of mitochondrial lipid peroxides were significantly reduced in mice treated with TRDF and TREF relative to LPS-fed mice. Furthermore, LPS caused induction of opening of the liver mPT pore which was significantly inhibited by TRDF at 100 and 200 mg/kg bw by 71% and 88%, respectively, but only at 100 mg/kg TREF. Furthermore, mitochondrial ATPase activity was inhibited largely by TRDF. UPLC–ESI–MS analysis revealed the presence of terpenoid derivatives and a few aromatic metabolites in TRDF. The terpene dominance of TRDF metabolites was further justified on the 1 H NMR fingerprint. Overall, TRDF is more effective as a cocktail of anti-inflammatory compounds than TREF against LPS-induced acute systemic inflammation.