Modern Advances in Pharmaceutical Research Vol. 3

TRP Channels in Physiological Nociception and Pain

Ivliane Nozadze — 2020-02-01

The Transient Receptor Potential (TRP) channel superfamily is comprised of a large group of cation-permeable channels, which display an extraordinary diversity of functions from sensory signaling to animal behaviors. These channels are ‘cellular sensors’ that respond to changes in the cellular environment, including temperature, stretch/pressure, chemicals, oxidation/reduction, osmolarity and pH, and of spices, venoms and toxins. The role of TRPs will be further elucidated in complex diseases of the nervous, intestinal, renal, urogenital, respiratory and cardiovascular systems. Although the physiological functions of most TRP channels are not well known, their wide distribution in cellular membranes indicates that the biological functions and activation mechanisms for these channels are diverse and important. In this paper we review our recent findings of activation different TRP channels evoked by chemical irritants such as cinnamon aldehyde and mustard oil for TRPA1, menthol for TRPM8 and capsaicin for TRPV1 by a battery of behavioral tests.

Evaluation of the Haemostatic Activities of Sida corymbosa in Rats

Lucy B. John-Africa — 2020-02-01

Aims: To evaluate the anti-haemorrhagic activity of the leaf extract of Sida corymbosa in Wistar albino rats, a plant used to arrest bleeding in ethnomedical practices.

Methods: The acute toxicity test was carried out in rats. The haemostatic activities of the extract were investigated using the tail bleeding time and amount of bleeding in rats; effects on haematological parameters were also evaluated in Wistar rats. Preliminary phytochemical analysis was conducted to detect the phytoconstituents of the extract of Sida corymbosa.

Results: In this study, the oral LD₅₀ of the extract was found to be greater than 5 g/kg. Administration of the extract to rats for 14 days produced a dose-dependent and significant (P≤0.05) decrease in bleeding time and quantity of blood loss in pre-treated rats. On oral administration of the extract, the effects of the treatment on haematological parameters – White blood cells, Red blood cell, haemoglobin concentration were not significantly different from control.

Conclusion: This study has shown that Sida corymbosa has constituents with anti-haemorrhagic properties in rats thereby providing scientific validation for the ethnomedical use of the plant in bleeding control.

Thermo-TRP Channels in Pain Sensation: An Overview

Merab G. Tsagareli — 2020-02-01

The perception of temperature is a major component of sensory experience of animal and human organisms. A sensitive response of the nervous system to changes in temperature is of predominant importance for homeo-therms to maintain a stable body temperature. Recent investigations in central and peripheral thermosensitivity have emphasized the importance of temperature-activated transient receptor potential (TRP) cation channels and they are being ardently pursued as targets for analgesic drug discovery. They are the largest group of sensory detectors expressed in nerve terminals and pain receptors activated by temperature and provide information about thermal changes in the environment. These temperature sensitive or thermo-TRP channels (TRPA1, TRPM8, TRPV1, TRPV2, TRPV3 and TRPV4) have been characterized to date that exhibit sensitivity to increases or decreases in temperature as well as to chemical substances that elicit similar hot or cold sensations. The thermal thresholds of many thermo-TRP channels are known to be modulated by extracellular mediators, released by tissue damage or inflammation. Antagonists or blockers of these channels are likely as promising targets for new analgesic drugs at the periphery and central levels and thus, controlling the modulation of thermo-TRP channels by inflammatory mediators and ligands may be a useful alternative strategy in developing novel analgesics.

Evaluation of Anti-diabetic Potentials of Methanol Extract of Ficus hispida Linn. Leaves against Alloxan Induced Diabetic Rats

V. D. Ravichandra — 2020-02-01

Objective: The present study was designed to evaluate the acute and chronic effects of the methanol extract of Ficus hispida against alloxan (150 mg/kg) induced diabetic rats.

Methods: In acute study, hypoglycemic potency of methanol extract of Ficus hispida was assessed by oral glucose tolerance test (OGTT) and in chronic study of 21 days, extract at different doses (ie 100, 200 and 400 mg/kg) was screened for its anti-diabetic activity. Blood glucose level had been estimated at 0, 7^th, 14^th and 21^st and addition to this serum concentrations of insulin, triglycerides, cholesterol, serum glutamate oxaloacetae transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and urea determined at 21^st day of the study.

Results: In OGTT, standard glibenclamide and extract (200 and 400 mg/kg) have shown significant reduction in blood glucose level compared to control group. In chronic model, the methanol extract was effective in reducing the blood glucose levels (P <0.001) at higher dose (200 mg/kg and 400 mg/kg) and effect was comparable to that of standard. The extract could also significantly (P<0.001) reduced level of SGOT, triglycerides and cholesterol in serum and significantly (P<0.001) increased the insulin level in blood which proves beneficial antidiabetic potentials of the extract in diabetic model. The change in concentrations of SGPT and urea were not significant (P>0.05).

Conclusion: The methanol extract of Ficus hispida posses significant anti-diabetic activity in alloxan induced diabetis in rats model.

Novel Simultaneous Separation and Quantitative Determination of Four Sartans in Presence of Hydrochlorothiazide by Isocratic RP-HPLC

Panchumarthy Ravisankar — 2020-02-01

A simple, reliable, sensitive, reproducible and novel isocratic RP-HPLC method was developed and validated for the separation and quantitative estimation of four angiotensin II-receptor antagonists namely Telmisartan (TELM), Losartan (LOSA), Olmesartan (OLME) and Valsartan (VALS) that are utilized in treating hypertension alone or along with some other drugs like thiazide diuretics mostly Hydrochlorothiazide (HCTZ). The key important benefit of developed method was that the five individual drugs can be determined on a single chromatographic system without alteration in detection wavelength and mobile phase. All the above said drugs were separated by using Welchrom C₁₈ column having internal diameter of 4.6 X 250 mm with 5 µm particle size as stationary phase with mobile phase consisting a mixture of acetonitrile and phosphate buffer (pH-3.3, 50:50 v/v). The mobile phase was pumped at a flow rate of 1 ml/min. The wave length of the UV detection was done at 238 nm. The total run time was eight minutes and the elution window of only three minutes. The calibration curves were linear (r² = 0.9998) in all cases. The relative standard deviation was less than 2% and average recovery was above 99.95%. This method was statistically validated in different parameters like linearity, precision, specificity, accuracy, robustness and ruggedness. The optimized method proved to be accurate, specific and robust for the quality control of four angiotensin-II receptor blockers alone or in combination with HCTZ in bulk drug and tablet dosage forms.

Prediction of Bitter Taste Receptor’s Active Site

Rafik Karaman — 2020-02-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the best treatment for conditions associated with pain, fever and inflammation. Non-steroidal anti-inflammatory drugs exert their therapeutic effects by blocking prostaglandin synthesis from arachidonic acid, which inhibits the activity of cyclooxygenases (COX-1 and COX-2). COX-1 is located in the stomach, kidney and other tissues, while COX-2 is located at inflammation sites. One of the disadvantages of the NSAIDs is their bitter sensation. This chapter discusses a novel approach to be used in the design of active sites of bitter taste receptors, especially TAS2R14, by using the X-ray crystal structure of the enzyme COX-2 and chemical structures of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) that bind effectively to COX enzymes and activate the bitter taste receptor TAS2R14. The suggested approach consists of docking calculations of the NSAIDs (ligands) to the active site of COX-2 and utilizing the data obtained in better understanding the nature of the interactions between bitter tastants and the chemical groups within the active site of TAS2R14 receptor.

Crosstalk between Mitochondria and Myofibrils in Adult and Aging Striated Muscle Tissue: Effect of Increased Functional Activity

Teet Seene — 2020-02-01

There has been much debate about changes of oxidative capacity in aging skeletal and heart muscle, and endurance capacity. Physiological changes during aging are associated with a decline in muscle mass, strength and endurance capacity. These changes in muscle structure and function are leading to disability in the aging population. The purpose of the present review is to discuss about decrease of oxidative capacity in adult and aging striated muscle tissue, changes in interaction between mitochondria and myofibrils and loss in life quality; describe the effect of increased functional activity (endurance exercise) on the oxidative metabolism. Decrease of endurance capacity (ability to keeo moving for longer time) during aging is related with reduced oxidative capacity of skeletal muscle due to decrease of mitochondrial biogenesis. Striated muscle cells with high oxidative capacity during endurance exercise hypertrophy. Muscle fibres with lower and low oxidative capacity do not hypertrophy during endurance type of exercise. Skeletal muscle respond to endurance exercise training by increasing the fibre composition towards increase of fibres with higher oxidative capacity at the expense of proportion of fibres with low oxidative capacity. Decease of oxidative capacity in muscle tissue lead to the decrease of muscle quality, cause disability and loss in life quality of aging population. Endurance exercise training is the effective way to increase the oxidative and endurance capacity.

Phytochemicals and Acute Toxicity of Moringa oleifera Roots in Mice

J. N. Kasolo — 2020-02-01

The phytochemicals used by plants to protect themselves against predators in Moringa oleifera roots were qualitatively identified in the aqueous and ethanol extracts. Its acute toxicity in 24 h was evaluated in Swiss albino mice. M. oleifera, a native plant of the sub-Himalayan tracts of India, Pakistan, Bangladesh and Afghanistan is used in folk medicine. It is claimed to have nutritional, medicinal, socio-economic and industrial values. Many individuals and families consume the roots for their medicinal properties. Despite wide use the roots, the phytochemicals and toxicity profile are not well documented. This study set out to determine the phytochemicals and acute toxicity of M. oleifera roots in mice. The roots were harvested during dry season and air dried. Serial extractions using ether, ethanol and water were done. The harvested phytochemicals were qualitatively identified using standard chemicals procedures. The phytochemicals identified were: Gallic tannins, catechol tennins, steroids and triterponoids, saponins, anthraquinones, alkaloids, and reducing sugars. Acute toxicity was determined by giving a single oral dose to Swiss albino mice and observed for 24 h. The LD₅₀ was calculated using the probit tables. The LD₅₀ of ethanol extract was 17.8 g/kg and that of aqueous extract was 15.9 g/kg. In conclusion, M. oleifera roots contain protective phytochemicals and are relatively non-toxic when given in a single dose.

Bitters: Time for a New Paradigm

Michael K. McMullen — 2020-02-01

In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: One involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.

Study with Medical Plants of Brazilian Amazon

Mayara Tania Pinheiro — 2020-02-01

In this chapter, studies on medicinal plants from the Amazon region on different experimental models were studied. Clearly and objectively addressing the popular use of these species, which justified the chosen models, botanical and phytochemical characteristics of the species. In addition, the results already published to the scientific community and future perspectives of the developed works will be exposed.

Reliability of the Direct Fluorescence Assay Compared to the Real-time RT-PCR as Respiratory Syncytial Virus Diagnostic Tool

Caroline F. Shafik — 2020-02-01

Lower respiratory tract infections (LRTIs) are the leading cause of morbidity and mortality among children under five years of age. Worldwide, Respiratory syncytial virus (RSV) is considered the most common cause of LRTIs among young children. There are various detection methods for RSV available in the market, two of them, the direct fluorescence assay (DFA) and the real-time reverse-transcription polymerase chain reaction (rt-RT-PCR) were compared in our study. The DFA provides same-day results, and the rt-RT-PCR is widely used in research laboratories because of its superior sensitivity; however, rt-RT-PCR is cost prohibitive in many clinical settings, particularly in newly industrialized and developing nations.

We collected 450 nasopharyngeal aspirates from children 5 years of age or less and tested for RSV using both methods. The overall prevalence rate of the RSV among the children was 23.8% with a significantly higher prevalence among children under the age of 6 months of age when compared to other age groups. The sensitivity of DFA in comparison to rt-RT-PCR was highest (86%) during the first 3 days of symptoms onset and decreased gradually till it reached 65% after the first week. The specificity of DFA in comparison to rt-RT-PCR ranged between 99 and 100% irrespective of the date of collection. We concluded that, although the rt-RT-PCR is more sensitive for RSV detection, the DFA offers a reliable point-of-care alternative detection method especially during the first few days of illness. Therefore, the DFA can be used as an early detection tool for RSV where rt-RT-PCR is unavailable.