Pharmacological Research - Natural Products最新文献

Aim of the study

To study the utility of Lawsone along with its zinc and copper complexes for wound healing activity using excision and incision wound models in rats.

Methods

The complex of plant nathoquinone from Lawsonia inermis called Lawsone viz Law and the metals viz. copper and zinc were synthesized. Molecular Docking (with GSK 3β protein) and Molecular Dynamic studies were carried out. The wound healing activity was evaluated using excision and incision wound models in Albino Wistar rats. The six groups comprised disease control, vehicle control, and standard, groups treated with Lawsone (Law) and its Zn Complex (ZnLaw) and copper complex (CuLaw). The progress of excision wound healing was monitored through wound contraction and biochemical and antioxidant parameters along with histopathology of granulation tissue, while for incision wounds, breaking and tensile strength were determined.

Results

The molecular docking studies revealed that ZnLaw has the highest affinity with GSK 3β protein. The Molecular Dynamic study determined the stability of Law and its metal complexes with GSK 3β protein and was found to be stable in the environment. The test compounds Law, ZnLaw, and CuLaw displayed significant (p<0.05) wound contraction. There was a significant (P< 0.01) decrease in the period of epithelisation as compared to vehicle control. ZnLaw showed maximum reduction in the period of epithelisation (16.03±0.942). There was a significant improvement in the antioxidant parameters from the granulation tissues of wounds treated with Law, ZnLaw, and CuLaw. The metal complexes of Law viz. ZnLaw and CuLaw showed a remarkable increase in hydroxyproline and hexosamine content as compared to the control. Histopathological findings indicated re-epithelisation, neovascularization, and increased collagen deposition as compared to the disease control. The incision model also revealed a significant (P< 0.001) increase in the tensile strength and breaking strength of the healed tissue as compared to the control.

Conclusion

Law and its Zinc and copper complexes exhibited good potential in healing of both incision and excision wounds.

Background

Glycyrrhizin, Curcumin and Piperine indicated good antiasthamatic properties owing to their ability to inhibit airways constriction and anti-inflammatory properties. Orodispersible tablets have advantage of faster drug release and has patient compliance in asthmatic patients.

Hypothesis / Purpose

To develop an orodispersible polyherbal tablets using the standardized extracts of Glycyrrhiza glabra, Curcuma longa and Piper nigrum with respect to glycyrrhizin, curcumin and piperine respectively and evaluate bioavailability of the markers from the formulation.

Methods

Alcoholic extracts of G. glabra, C. longa, and P. nigrum were standardized using HPTLC for glycyrrhizin, curcumin, and piperine content, respectively. The orodispersible tablet formulation was created and standardized for curcumin (50 mg), glycyrrhizin (75 mg), and piperine (2.5 mg) per tablet, using the HPTLC method. The absolute Bioavailability studies were conducted for glycyrrhetinic acid and curcumin in rats by administering pure marker compounds intravenously (2 mg/kg b.w) and orally (10 mg/kg b.w.), followed by determining relative bioavailability through oral administration of the orodispersible tablet formulations.

Results

Orodispersible tablets could be successfully developed using the standardized extracts. The HPTLC bioanalytical method was developed and validated as per M 10 guideline and results were in accordance to specifications. The bioavailability studies in rats indicated absolute bioavailability of Glycyrrhetinic acid and Curcumin to be 20.35 and 2.57% respectively and relative bioavailabilities of orodispersible formulation F1 were found to be 75 and 38.67%.

Conclusion

A standardized orodispersible formulation can be a better option for asthma patients. The low absolute bioavailability of curcumin was significantly (P<0.05) increased in both the formulations F1 and F2. This may be attributed to the extracts containing saponin glycosides like Glycyrrhizin aiding into greater dissolution of curcumin. Formulation with piperine (F1) showed significant increase in bioavailability is due to inhibition of human P-glycoprotein, cytochrome P450 3A4 (CYP3A4) and increase secretion of bile acids.

Introduction

Eucalyptus plants are used as a source of essential oils in Ethiopia and are traditionally used for the treatment of the common cold, stomachache, swelling and wounds. This study aims to determine the chemical composition and antibacterial activity of the essential oils of E. camaldulensis Dehn. and E. tetragona Muell.

Methodology

The chemical composition of the essential oils of E. camaldulensis Dehn. and E. tetragona F.Muell. was determined using gas chromatographymass spectrometry (GCMS), and their antibacterial activity of was evaluated against E. coli ATCC 25922 and S. ATCC 25923.

Results

The yield of essential oil from the leaves of E. camaldulensis was 0.72% w/w, and the yield of essential oil from the leaves of E. tetragona was 0.80% w/w on the basis of fresh leaf weight. A total of 17 and 14 components were identified in E. camaldulensis and E. tetragona, respectively. The main components identified were 1,8-cineole, β-cymene and α–pinene in both Eucalyptus species analysed. The extracted essential oils displayed moderate to strong antibacterial activity. E. tetragona inhibited S. aureus at a lower concentration (0.625 μg/ml), while E. coli was less sensitive to the EOs of E. camaldulensis, with an MIC of 2.5 μg/ml.

Conclusion

The essential oils of E. camaldulensis and E. tetragona exhibited significant antibacterial activity against E. coli and S. aureus. The results showed that the essential oils of E. camaldulensis and E. tetragona may be useful for treating various infectious diseases. Essential oils, particularly 1,8-cineole, can be used as alternative natural antimicrobial agents in the pharmaceutical and food industries.

Background

Regulation of balance between vasoconstriction and vasodilation has become a therapeutic target to vascular complications. However, Aluminium chloride, a naturally abundant environmental toxicant has been reported to disrupt this balance via increased oxidative stress and inflammation in several studies. Whether Peperomia pellucida, a popular medicinal plant known for its pharmacological benefits can modulate vascular tone in mice exposed to aluminium chloride is yet to be unravelled. This study investigated the effect of Peperomia pellucida ethanol leaf extract on aluminium chloride induced vascular dysfunction in male Swiss mice.

Methods

Phytochemical profiling of Peperomia pellucida was done using GC-MS and vascular effect of Peperomia pellucida was investigated by administering 50 mg and 100 mg of the extract alongside aluminium chloride orally for 14 days. Aorta was harvested for biochemical (SOD, CAT, GSH, MDA, nitrites), ELISA (endothelin-1, TNF-α and IL-6) assays as well as immunohistochemical studies (occludin and caspase-3).

Results

GC-MS profiling showed 8 phytocompounds with 3,5-Dimethoxybenzamide as the highest peak area. Antioxidant armouries such as SOD catalase, glutathione as well as vascular occludin expression was significantly enhanced by Peperomia pellucida (50 mg/kg and 100 mg/kg) against aluminium chloride perturbations while suppressing TNF-α, IL-6, ET-1 activities and caspase-3 expression against increase caused by aluminium chloride intoxication.

Conclusion

Our result showed that Peperomia pellucida leaf extract modulated vascular tone via antioxidant, anti-inflammatory and ant-apoptotic properties which was mediated by its phytocompounds

Acrylamide, a ubiquitous industrial chemical, and food contaminant, has been implicated in various toxicological effects, including biochemical, hematological, and histological alterations. In this study, we investigated the potential protective effects of caffeic acid against acrylamide-induced toxicity in a rat model. Rats were divided into three different groups, including a control group, an acrylamide-exposed group (19.13 mg/kg), and groups treated with acrylamide (19.13 mg/kg for 28 days) + caffeic acid (20 mg/kg after 28 days exposure to acrylamide). Biochemical parameters, hematological indices, and histopathological changes were systematically evaluated to assess the impact of acrylamide and the ameliorative effects of caffeic acid. Our results revealed that acrylamide exposure led to significant alterations in biochemical markers, hematological and serological parameters, and histological architecture in liver, kidney, and brain tissues. However, administration of caffeic acid demonstrated attenuation of these adverse effects. The protective effects of caffeic acid were evident through the restoration of key biochemical parameters, maintenance of hematological and serological homeostasis, and preservation of tissue histology. Furthermore, our findings suggest that caffeic acid may exert its protective effects through antioxidant mechanisms, as evidenced by the reduction in oxidative stress markers. In conclusion, this study provides comprehensive insights into the protective potential of caffeic acid against acrylamide-induced biochemical, hematological, serological, and histological alterations in rats. The observed ameliorative effects underscore the therapeutic potential of caffeic acid as a promising adjunct in mitigating the toxicological consequences of acrylamide exposure.

The objective of the study was to isolate and characterize phytochemicals from the stem extract of D. reflexa and investigate their biochemical activities. Five flavonoids together with two terpenoids, were isolated. Their structures were identified using 1D and 2D nuclear magnetic resonance (NMR) and mass spectroscopic techniques in combination with circular dichroism (CD) spectroscopy, as well as comparisons with published data. The in vitro reactive oxygen species scavenging potential of the compounds was investigated. The lipoxygenase and urease inhibitory potential of the compounds were tested using in vitro and in silico methods. Compound 1 and 2 exhibited potent antioxidant activity with lower IC₅₀ values of 38.5 ± 0.25 and 39.5± 0.14 μM respectively compared with the standard used (BHA IC₅₀ value = 39.5± 0.14) in DPPH assay. Compound 1 and 2 also exhibit good reducing ability and superoxide radical scavenging activity reflected by IC₅₀ value 44.6 ± 0.30 and 48.5 ± 0.16 respectively compared with BHA (IC₅₀ 45.6 ± 0.54). Compound 2 and 3 showed significant inhibitory effect against urease with IC₅₀ values 26.2 ± 0.29 μM and 36.5 ± 0.37 μM respectively, while compound 4 with IC₅₀ value 33.3 ± 0.74 μM is the most active against lipoxygenase. All the seven compounds showed varying degrees of binding affinity against the targets with compounds 1–5 having the better docking score compared with the co-crystalized ligands of both lipoxygenase and urease. The density functional theory reveals the replicate of the transitional state between the compounds and their respective receptor and stability of the compounds was predicted from the energy gap (E_LUMO – E_HOMO). These compounds are potential drug against stomach ulcers, inflammation and oxidative stress associated diseases. It is also worth mentioning that the complete assignments of NMR data 1 and 2 were reported for the first time in this study.

Ethnopharmacological relevance

Cleome droserifolia treatment has potent antioxidant, antimicrobial, and immunomodulatory potentials, which can help recover the general health status.

Aim of the study

This research aims to estimate the potential cardioprotective properties of the methanolic extract of Cleome droserifolia (MEC) against epinephrine-induced cardiac injury (MI) in rats.

Materials and methods

Thirty-six male Wistar rats were separated equally into 6 groups. The control group (Cont) received oral distilled water for 30 uninterrupted days and was administered subcutaneous saline on the 31^st and 32^nd days. The MEC 100 group received MEC 100 mg/kg, P.O., for 30 uninterrupted days and administered subcutaneous saline on the 31^st and 32^nd days. The MEC 200 group received MEC 200 mg/kg, P.O. for 30 uninterrupted days and subcutaneous saline was administered on the 31^st and 32^nd days. The epinephrine group (EP) received distilled water orally for 30 uninterrupted days and administered subcutaneous epinephrine (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31^st and 32^nd days. MEC 100+Ep group received MEC 100 mg/kg, P.O., for 30 uninterrupted days and administered subcutaneous epinephrine (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31^st and 32^nd days. The MEC 200+EP received MEC 200 mg/kg, P.O. for 30 uninterrupted days and administered subcutaneous epinephrine (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31^st and 32^nd days. Electrocardiography (ECG), biochemical, oxidative stress, inflammatory mediators, histopathological, immunohistochemical analysis and the expression of phosphoinositide 3-kinases (PI3K) and protein kinase B (AKT) were assessed.

Results

MEC reversed epinephrine-induced lessening of heart rate, prolonged QT interval and ST displacement. Pretreatment with MEC significantly reduced serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels in MI rats. The MEC pretreatment promoted total antioxidant capacity (TAC), glutathione (GSH), and total oxidant status (TOS). In addition, it reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), malondialdehyde (MDA), and tumour necrosis factor (TNF-α) in MI rats. Furthermore, MEC statistically reduced immunohistochemical promotion of nuclear factor–κB (NF-κB) and expression of AKT and PI3K in cardiac tissue and perfected histopathological changes.

Conclusion

The MEC, rich in phenolic and flavonoid contents, had a cardioprotective effect on rats suffering from epinephrine-induced MI. Such effect was achieved via improving cardiac function, antioxidant status, attenuating ECG pattern and histological picture, as we