Effect of aged garlic extract and s-allyl cysteine and their interaction with atenolol during isoproterenol induced myocardial toxicity in rats

Objectives:

The study evaluates the cardioprotective effect of aged garlic extract (AGE) and its constituent; S-allylcysteine (SAC) and their interaction with atenolol during isoproterenol induced cardiac toxicity in rats.

Materials and Methods:

Rats were administered AGE at two different doses of 2 ml/kg or 5 ml/kg orally whereas SAC was administered either at a dose 13.1 mg/kg or 32.76 mg/kg. The AGE or SAC was given alone or in combination with atenolol (6 mg/kg, p.o), every alternate day for three weeks. At the end of treatment, two doses of isoproterenol (150 mg/kg, s.c) were administered to rats. The electrocardiogram (ECG) was recorded followed by withdrawal of blood to estimate serum lactate dehydrogenase (LDH) and creatinine kinase-MB (CK-MB) activities. The activities of LDH, CK-MB as well as superoxide dismutase (SOD), catalase and thiobarbituric acid reactive substances (TBARS) were also determined in the heart tissue homogenate (HTH).

Results:

The isoproterenol induced ECG changes were restored to normal in all treated groups. The AGE and SAC administration caused a decrease in serum LDH and CK-MB activities and an elevation of LDH and CK-MB activities in HTH. Atenolol alone or in combination with AGE and S-allylcsyteine demonstrated similar changes in biomarker activities.

Conclusion:

AGE showed dose-dependent cardioprotection. However, concurrent administration of SAC with atenolol (6 mg/kg, p.o) combated more effectively the myocardial dysfunction during isoproterenol induced cardiotoxicity in rats.KEY WORDS: Acute myocardial injury, aged garlic extract, atenolol, isoproterenol s-allyl cysteine     

The Effect of Tropical Environment on Fatigue Failure in Royal Malaysian Airforce (RMAF) Aircraft Structure and Operational Readiness

The environmental condition in which the Royal Malaysian Airforce is currently operating its aircraft is prone to corrosion. This is due to the high relative humidity and temperature. With most of its aircraft being in the legacy aircraft era, the aircraft’s main construction consists of the aluminium 2024 material. However, this material is prone to corrosion, thus reducing fatigue life and leading to fatigue failure. Using the concept of either Safe Life or Damage Tolerance as its fatigue design philosophy, the RMAF adopts the Aircraft Structure Integrity Program (ASIP) to monitor its structural integrity. With the current problem of not having the structural limitation on corrosion-damaged structure, the RMAF has embarked on its fatigue testing method. Finite Element (FE) studies and flight tests were conducted, and the outcome is summarized. The conclusion is that the longeron tested on the aircraft can withstand the operational load, and its yield strength is below the ultimate yield strength of the material. These research outcomes will also enhance the ASIP for other aircraft platforms in the RMAF fleet for its structure life assessment or service life extension program.     

Structure-Function Analyses of New SARS-CoV-2 Variants B.1.1.7, B.1.351 and B.1.1.28.1: Clinical,Diagnostic, Therapeutic and Public Health Implications

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.     

Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.     

Two-stage mass spectrometry approach for the analysis of triterpenoid glycosides in Fagonia indica

Triterpenoid glycosides are molecules widely distributed in plants and have shown a wide range of biological activities against various diseases. This paper describes the qualitative and quantitative analysis of triterpenoid glycoside (saponins) using a two-stage mass spectrometry approach in five samples of Fagonia indica collected from various parts of the country. In the first stage, triterpenoid glycosides were identified using liquid chromatography high-resolution mass spectrometry using UHPLC-QTOF-MS system. In the second stage, compounds were quantified using a multiple reaction monitoring (MRM) approach using an UHPLC-QQQ-MS system. Fagonia indica has shown a wide range of biological activities and found to be rich in saponin or triterpenoid glycoside constituents. A total of thirteen triterpenoid saponins were identified based on high-resolution analysis, MS/MS and database comparison, while six of them were simultaneously quantified using the multiple reaction monitoring (MRM) approach. The results indicate that the samples share a similar UHPLC pattern, however, the amount of these saponins in samples varies greatly. Compound 4i.e. nayabin D was the major constituent (1.4–3.8 μg g⁻¹) among the six analyzed compounds. The results demonstrated that the developed multi-compound determination in combination with a fingerprint analysis method is rapid, accurate, precise and sensitive and can be utilized for quality control and high-throughput quantification of various saponins in Fagonia indica may be extended to other plant species.

Development of a rapid, accurate, precise, and effective method for the analysis and quantification of saponins in crude extracts from Fagonia indica.