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Euphorbia prostrata (E. prostrata) and Crotalaria burhia (C. burhia) are widely found in flora of the Cholistan Desert of Bahawalpur, Pakistan and are traditionally used to treat pain and chronic disease. The current study aimed to evaluate their phytochemical screening, antioxidant activity, in-vivo phagocytic activity, and analgesic activity. Both the plant extracts were investigated for phytochemical screening, Fourier Transform Infrared (FTIR) analysis, in-vitro antioxidant by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method, in-vivo immunomodulatory activity by macrophages phagocytosis using carbon clearance rate assay and analgesic activity by acetic acid produced writhing method. Phytochemical screening showed the presence of carbohydrates, saponins, tannins, phenols, quinines, proteins, terpenes, glycosides, and alkaloids. FTIR analysis revealed the existence of different functional groups in both extracts. The DPPH method showed that E. prostrata exhibited a high antioxidant potential with an IC50 of 62.5 µg/ml whereas C. burhia showed a lower antioxidant potential. At the dose of 200 mg/kg body weight (b. wt), both the extracts showed a significant increase in the phagocytic index by 5.2 ± 0.2, and, 4.8 ± 0.1 (p < 0.001) respectively which was close to the 100 mg/kg b. wt of the standard drug (Levamisole) 5.4 ± 0.2. Both the extracts at the dose of 200 mg/kg b. wt also significantly reduced the writhing (abdominal contractions) count by 13.7 ± 0.3 and, 25.3 ± 1.5 (p < 0.001), showing 71.8% and 47.6% of reduced analgesic activity compared to the standard drug dicloran (diclofenac sodium), respectively. In conclusion, extracts of both plants indicate their role in the management of various disorders to relieve pain and modulate the immune system.

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Herein, Imiquimod (IMQ) was incorporated in nanotransethosomes (nTES) to develop the IMQ-nTES nano-drug delivery system. IMQ-nTES was optimized using 23 factorial design. The optimized formulation was expressed with a particle size of 192.4 ± 1.60 nm, Poly-dispersibility of 0.115 ± 0.008, and IMQ percent entrapment efficiency of 91.05 ± 3.22%. Smooth and round morphology of IMQ-nTES vesicles was confirmed by TEM micrographs. Moreover, FTIR results have shown drug-excipient compatibility. The IMQ-nTES was laden inside the low molecular weight chitosan gel, which exhibited easy application, spreadability and no irritation to the applied skin. The release pattern has clearly exhibited improved dissolution properties of IMQ with the provision of the sustain release pattern. Higher IMQ content was deposited in deeper epidermis and dermis with IMQ-nTES gel, in contrast to ALDARA. In vivo, comparative toxicity study on BALB/c mice has shown significantly reduced (p < 0.001) psoriatic area severity index (PASI) score and less increment in ear thickness. Epidermal hyperplasia was an obvious finding with ALDARA which was, providentially, minimal in IMQ-nTES gel-treated skin. FTIR analysis of skin tissue has shown an enhancement of lipid and protein content in the ALDARA group, however, in the IMQ-nTES group no such change was observed. With ALDARA application, CD4+ T-cells and constitutive NF-κß expression were significantly elevated, in comparison to the IMQ-nTES gel treated group. Moreover, the adequate expression of IFN-γ and cytotoxic CD8+ T-cells were suggesting the preserved IMQ efficacy with IMQ-nTES gel. Quantification of cutaneous as well as systemic inflammatory markers has also suggested the reduced psoriatic potential of IMQ-nTES gel. In essence, IMQ-nTES gel can be a suitable alternative to ALDARA owing to its better safety profile.

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The current study was carried out to explore the phytochemical, antioxidant potential and antibacterial activities of the crude methanolic extract of A. santolinifolia Turcz. Ex Besser. The antioxidant activity was carried out by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) assay, while methanolic extract displayed the highest scavenging activity (DPPH) was 61.31µg/ml on Artemisia santolinifolia root and the lowest (51.05µg/ml) was record for their leaves. Similarly, in (ABTS) the highest activity (89.16µg/ml) was recorded for roots of A. santolinifolia followed by leaves (68.14µg/ml). In low inhibitory concentration assay, the crude methanolic extracts showed significant inhibition against all tested microbes on different concentrations like 25 µg/ml, 50 µg/ml, and 100 µg/ml. The leaves extract of A. santolinifolia AsL showed MIC of 12.5µg/ml for B. subtilis, a gram-positive bacterium, 50µg/ml for gram positive bacteria S. aureus and 37.5 µg/ml for gram negative bacteria P. aeruginosa that is almost equal to the response of standard ciprofloxacin. Our current study revealed that Artemisia santolinifolia root (AsR) exhibited a significant antioxidant potential while AsL showed good antibacterial effect which is suggested to be used for treatment and management of different infectious diseases.

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Cancer is one of the most leading causes of death and a major public health problem, universally. According to accumulated data, annually, approximately 8.5 million people died because of the lethality of cancer. Recently, a novel RNA domain-containing endonuclease-based genome engineering technology, namely the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9) have been proved as a powerful technique in the treatment of cancer cells due to its multifunctional properties including high specificity, accuracy, time reducing and cost-effective strategies with minimum off-target effects. The present review investigates the overview of recent studies on the newly developed genome-editing strategy, CRISPR/Cas9, as an excellent pre-clinical therapeutic option in the reduction and identification of new tumor target genes in the solid tumors. Based on accumulated data, we revealed that CRISPR/Cas9 significantly inhibited the robust tumor cell growth (breast, lung, liver, colorectal, and prostate) by targeting the oncogenes, tumor-suppressive genes, genes associated to therapies by inhibitors, genes associated to chemotherapies drug resistance, and suggested that CRISPR/Cas9 could be a potential therapeutic target in inhibiting the tumor cell growth by suppressing the cell-proliferation, metastasis, invasion and inducing the apoptosis during the treatment of malignancies in the near future. The present review also discussed the current challenges and barriers, and proposed future recommendations for a better understanding.

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Androsace foliosa is a medicinal herb utilized in different areas of Pakistan for abortifacient, diabetic and liver complications. In the current research, the possible action of the n-hexane leaves extract of the Androsace foliosa on isolated rabbit uterus was examined. Abortifacient activity was examined in the existence of standard antagonist e.g. atropine and salbutamol and a uterine tonic like oxytocin. The isolated rabbit uterus is initially treated with 1mg/kg stilboesterol for 1 complete day. The consequence of oxytocin as uterine contraction agonist was observed. Additionally, antagonists e.g. salbutamol (2µg) and atropine (1-2mg) on the uterine contractile action of the extract were also examined. The A. foliosa n-hexane leaves extract fashion dose correlated amplification in the force of uterine contraction comparable to oxytocin. The drug oxytocin was pragmatic to amplify the uterine contractile action of the extract. Meanwhile pre-treating the tissue with either atropine or salbutamol earlier than administrating the extract indicates the inhibitory action of the drugs on the action of the extract.

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Ivy leaf is used for the treatment of respiratory diseases with the intensive mucus formation, respiratory infections, and irritating cough coming from the common cold. Conferring to clinical trials, the efficacy, and tolerability of ivy leaf is good. The main compounds accountable for biological activity are triterpene and saponins. Ivy leaves show convulsive/antispasmodic, anti-inflammatory, antimicrobial, analgesic, anthelmintic and anti-thrombin activity. Not only ivy but also marshmallow and mustard seeds are used for these indications. This study was conducted to evaluate the efficacy and safety of Cough (EMA; European Medicines Agency) granules used for upper respiratory disorders. This clinical trial was conducted on 150 patients, out of which 75received the Cough (EMA) granules and 75received the placebo. The age range of patients was 3 years to above 15 years. The sample paired t-test was applied to evaluate the significant level. Cough (EMA) granules were found effective in the treatment of cough, cold, and flu symptoms. The new treatment Cough (EMA) granules were safe and well tolerated in patient at given specific age group. The study recommends that Cough (EMA) granules can be used effectively in the treatment of upper respiratory tract infection.

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Thallium has been shown to significantly influence various tissues of living organisms; Exposure to Thallium can disturb mitochondrial function, degenerate neurons, and interfere with the function of critical metabolic enzymes and co-enzymes. Glutathione (GSH) an essential biomarker is considered a key factor in harnessing the thallium toxicity. In the present study the interaction of Thallium (Thallium Chloride) and glutathione was investigated spectro-photo-metrically in aqueous media. The renowned Elman's experimental protocol was followed at a wavelength of 412nm for Glutathione quantification in each sample. The pH of each sample was maintained at 7.6 using Phosphate buffer during the entire course of the experiment. A concentration as well as time dependent depletion of glutathione after exposure to various concentration of Thallium metal was observed, revealing chemical interaction between the metal and glutathione. The exact mechanism of interaction of Thallium and glutathione is still to be investigated. However, this piece of research suggests that a decrease in the concentration of Glutathione may be due to Thallium-GSH abduct or oxidize glutathione (GSSG) formation. This study was performed in-vitro as a model of in vivo.

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Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity. Angiotensin II Receptor Antagonists/Blockers (ARBs) compete with angiotensin II at the receptor site and block the contractile effect of angiotensin II in all vascular smooth muscles. Among all Angiotensin II Receptor Antagonists/Blockers (ARBs), Telmisartan, Milfasartan and many others have benzimidazole ring in their structure. In this study Angiotensin II Receptor Antagonists/Blockers (ARBs) have been prepared. Synthesized compounds were characterized by physical data and FTIR spectroscopic technique. Synthesized compounds studied were finally screened for their antihypertensive activity by tail cuff method of measurement of blood pressure by NIBP apparatus (None Invasive Blood Pressure) using Chart 5.0 software. The compounds synthesized were 2-(3-nitrophenyl)-1Hbenzimidazole (1a), 3-(1H benzimidazol-2-yl)aniline (1b) and 5-(1H-benzimidazol-2-yl)-2-methoxyphenol (1c). The synthesized compounds have shown antihypertensive activity by taking Losartan as lead compound.

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Glutathione is an essential antioxidant of living organism that provides a primary protection against metals toxicity. A significant amount of glutathione is present in blood erythrocytes, plasma and liver hepatocytes to protect them from oxidative damage from both external and internal oxidants. Metalo-element palladium has numerous pharmacological, clinical and toxicological compensations, like palladium is used as anti-viral, anti-bacterial, neuro-protective and anti-tumor agent. However studies have also indicated some mild to serious toxic effects of palladium metallo-elements. In the presence study the interaction of palladium inorganic salt and organic complex with glutathione (GSH) content of liver homogenate was examined spectro-photometrically. 20% (w/v) liver homogenate was prepared of the collected liver of rabbit in 5% TCA (tri-chloro-acetic acid) solution and 1mm EDTA, using a potter-eveljhem homogenizer with motor driven Teflon pestle. The GSH content quantification was carried out by Elman's method. Our finding showed that there was a depletion of GSH content by both palladium inorganic salts and organic complexes, concentrations wise as well as with time elapse as level of GSH content decrease from (43.6% to 72.62%) with Palladium Nitrate and from (24.09 to 59.5%) with Bis-benzonitrile Palladium II Chloride as compared to control, and further dropped with time incubation from 0-90 minutes from (49.7 to 87.1%), with Palladium Nitrate and from (29.3% to 67.6%) respectively. The result showed that the effect of both inorganic salt of palladium was more enhanced as compare to its organic complex. It was suggested from our finding that the depletion in the glutathione content of liver homogenate may be due to oxidation of glutathione or due to glutathione metal abduct formation by both inorganic salt and organic complex of palladium. This study in situ is a model of in vivo.

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The metalloelement Palladium has a number of potential Pharmaco-clinical advantages. Palladium compounds have antiviral, antibacterial, neuroprotective and antitumor properties. However studies have also indicated some mild to serious toxic effects of Palladium metalloelements. Biothiols are important antioxidants that provide protection against metals toxicity. The interaction of metalloelements with biothiols can provide valuable information about the level of toxicity of the metalloelements and about the protective role of biothiols thereof. In this piece of work the effect of salt and complexes of Palladium on the status of different thiols (GSH, NAC, and D-Pen) in aqueous medium, were examined, The thiol quantification was carried out using Elman's method through UV-visible spectrophotometry and 1H- NMR. Results of the study performed in aqueous medium showed that level of different thiols depleted after the addition of the inorganic salts and organic complexes of Palladium. The mechanism of interaction of Palladium with thiols was examined using H-NMR. The results indicate that the depletion in the level of thiols may be due to 1:1 or 1:2 conjugation of Palladium with thiols. These conjugation reactions further suggest that the Palladium have xenobiotic nature causing oxidative stress and thiols play their role in detoxification and biotransformation of these metalloelements.

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Thiol groups are extensively present across biological systems being found in range of small molecules (e.g. Glutathione, Homo-cysteine) and proteins (e.g. albumin, haemo-globin). Albumin is considered to be a major thiol containing protein present in circulating Plasma. Albumin contains a single thiolate group located at cysteine-34(cys-34) at its active site. Albumin also binds a wide variety of metals and metals complexes at various sites around the protein. Usually heavy metals are preferentially attached with the thiol group of albumin. The binding of heavy metals at cys-34 provides a mechanism by which the residence time of potentially toxic species in the body can be increased. In this research we have assessed the oxidative modification of and metal binding capacity of cys-34 with heavy metals Palladium and Vanadium to investigate the ease with which it is possible to effect disulfide-thiol exchange at this sites/or remove a metal bound at this position. Both the metals were treated with albumin and then the albumin metals (Pd and V) complexes were treated with small thoil molecules like Glutathione, Cysteine and D-Penicillamine. Our finding showed that the albumin thiol group retained the metals with itself by forming some strong bonding with the Thiols group, it is concluded from this finding that if by chance both the metals enter the living system; strongly disturb the chemistry and physiological function of this bio-molecule.

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Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity.

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This piece of research work present the toxicological impact of varied concentrations of palladium nitrate [Pd (NO3)2] by changing the chemical status of glutathione and the way how glutathione plays its role in detoxification and conjugation processes of [Pd (NO(3))(2))] in whole blood components (plasma and cytosolic fraction). The impact of different concentration of [Pd (NO3)2] on reduced glutathione level in whole blood component (plasma and cytosolic fraction) were measured spectrophotometrically following Standard Ellman's method. Compared with control sample, significant decrease in the GSH content in whole blood components (plasma and cytosolic fraction) was obtained with various concentrations (100µM-1000µM) of palladium nitrate. Depleted GSH level was more pronounced with time incubation period (0-90) minutes. These finding shows that changes in the GSH status produced by palladium nitrate could either be due to palladium nitrate and glutathione( Pd-SG) complex formation or by conversion of reduce glutathione (2GSH + Pd(+2) - GSSG). This change in the GSH metabolic status provides information regarding the mechanism of palladium, in blood components.

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Metallo-elements including Vanadium (V) have strong affinity for sulfhydryl (-SH) groups in biological molecules including Glutathione (GSH) in tissues. Because of this fact it was of interest to further investigate the interaction of Ammonium Vanadate [NH(4)VO(3)] with Glutathione as a biomarker of toxicity and the role of Glutathione in the detoxification and conjugation pr(o)Cesses in whole blood components including plasma and cytosolic fraction. Effects of different concentrations of Ammonium Vanadate [NH(4)VO(3)] on the level of reduced Glutathione in whole blood components (Plasma and Cytosolic fraction) were examined. GSH depletion in plasma and cytosolic fraction was Ammonium Vanadate's concentration-dependent. Depleted GSH level was more pronounced with more incubation time period. These findings show that changes in the GSH status produced by Ammonium Vanadate could be due to either by adduct formation of Vanadium and glutathione i.e. (V-SG) or by increased production of oxidized Glutathione (2GSH +V(+5) → GSSG). This change in GSH metabolic status provides some information regarding the mechanism of toxicity by Ammonium Vanadate and the protective role of glutathione.

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Mercury is harmless in an insoluble form, such as mercuric sulfide, but it is poisonous in soluble forms such as mercuric chloride or methylmercury. Mercury is a neurotoxin. Outbreaks of mercuric chloride poisonings have made it clear that adults, children, and developing fetuses are at risk from ingestion exposure to mercury. It is very important and interesting to study the reaction of mercuric chloride and Glutathione as biomarker of Glutathione role in detoxification and conjugation in components (Plasma and Cytosolic Fraction). The effect of mercuric chloride's different concentrations was examined on GSH present in plasma and cytosolic fraction. Decrease in GSH level was dependant on mercuric chloride concentration. The decrease in GSH level of blood components was more prominent with the time of incubation of mercuric chloride. Decrease in the concentration of reduced state Glutathione may be due the interaction of reduced state Glutathione (GSH) and mercuric chloride to form oxidized Glutathione (GSSG) or mercuric-glutathione complex. This change in GSH metabolic status provides information regarding the role of GSH in detoxification of mercuric chloride. The effect of mercury metal on Glutathione in blood components has been discussed in this paper in vitro condition as a model for in Vivo condition.

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