Isolation of a novel isoprenylated phenolic compound and neuroprotective evaluation of Dodonaea viscosa extract against cerebral ischaemia-reperfusion injury in rats.

Dodonaea viscosa grows widely in Saudi Arabia, but studies evaluating its neuroprotective activity are lacking. Thus, this study aimed to isolate and identify the secondary metabolites and evaluate the neuroprotective effects of D. viscosa leaves. The isolation and identification of phytochemicals were performed using chromatographic and spectroscopic techniques. The neuroprotective potential of the extract was evaluated against focal cerebral ischaemia-reperfusion injury in rat model. Neurobehavioural deficits in the rats were evaluated, and their brains were harvested to measure infarct volume and oxidative biomarkers. Results revealed the presence of three compounds: a novel isoprenylated phenolic derivative that was elucidated as 4-hydroxy-3-(3'-methyl-2'-butenyl) phenyl 1-O-ß-D-apiosyl-(1''' â†’ 6'')- ß-D-glucopyranoside (named Viscomarfadol) and two known compounds (isorhamnetin-3-O-rutinoside and epicatechin (4-8) catechin). Pre-treatment of the rats with the extract improved neurological outcomes. It significantly reduced neurological deficits and infarct volume; significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels; and significantly elevated antioxidant (superoxide dismutase, catalase, and glutathione) activities. These results indicate that D. viscosa is a promising source of bioactive compounds that can improve neurological status, decrease infarct volume, and enhance antioxidant activities in rats with cerebral ischaemic injury. Thus, D. viscosa could be developed into an adjuvant therapy for ischaemic stroke and other oxidative stress-related neurodegenerative disorders. Further investigations are warranted to explore other bioactive compounds in D. viscosa and evaluate their potential neuroprotective activities.

Chemical constituents from Centaurothamnus maximus and their antimicrobial activity.

A new sesquiterpene lactone, 3ß,10α-dihydroxy-10ß-(hydroxymethyl)-8α-(4-hydroxymethacrylate)-1αH,5αH,6ßH,7αH-guai-4(15), 11(13)-dien-6,12-olide (1), along with twenty-one known compounds, were identified from the aerial parts of Centaurothamnus maximus. The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (2, 3, 5‒13 and 15‒22) were identified from C. maximus for the first time. Antibacterial and antifungal activities of the isolated compounds were tested using the agar disc diffusion method. Compounds that demonstrated promising antimicrobial activity were evaluated for their minimum inhibitory concentration (MIC). The results showed that compounds 3 and 7 were the most effective antibacterial compounds against B. subtilis ATCC 6633, S. aureus ATCC 25923 and S. pyogenes ATCC 27736, with MIC estimates between 8 and 32 mg/mL. In addition, compound 2 exhibited the strongest antifungal activity against C. albicans ATCC 14243 and C. krusei ATCC 14243 with MIC 8 mg/mL.

Twenty-two compounds were first isolated from Centaurothamnus maximusThe structure of the new sesquiterpene lactone, thamnolide (1), was established.Antibacterial and antifungal activities were tested for the isolated compounds.Compounds 3 and 7 were the strongest antibacterial compounds whilst 2 exhibited the strongest antifungal activity.

Attitudes and Associated Demographic Factors Contributing towards the Abuse of Illicit Drugs: A Cross-Sectional Study from Health Care Students in Saudi Arabia.

Background and objective: The purpose of this study is to compare the attitudes, views, and factors that influence drug abuse among pharmacy and nursing students at a Saudi Arabian university. Materials and Methods: A cross-sectional study, was conducted among pharmacy and nursing students who are currently enrolled in the respective courses at the study site. The data were collected over 4 months from August to November 2019 using structured self-administered paper-based questionnaires. Results: Among the participants, pharmacy students accounted for 184 (58.2%) while 132 (41.8%) of the students were from nursing. More than a third of the students 129, (40.8%) smoked cigarettes. The majority of pharmacy (80.4%) and nursing students (67.4%) reported having undertaken a drug misuse course in college. Among the participants, 132 (41.7%) stated that an offer from friends, followed by joy seeking 129 (40.8%), parents' divorce 126 (39.8%), having access to drugs 125 (39.5%), family issues 110 (34.8%), 66 (20.8%) having a family member who is addicted, and 101 (31.9%) reported curiosity to be the factors regarding the use of abusive drugs. Transient euphoria (75.9%) followed by depression 197 (62.3%) was the most prevalent physical or psychological change that occurred following drug use. The family size and father's education have significantly affected the attitudes scores of the students (F = 5.188; p = 0.0001). Conclusion: In this study, joy-seeking, access to drugs, and family issues were found to be the major factors listed as reasons for drug abuse, with some of them being controllable or reversible. Educating about the adverse outcomes of abused drugs is warranted.

Amelioration of Experimental Hepatotoxicity in Rats by Portulaca oleracea Linn. from Kashmir Himalaya.

BACKGROUND: Traditionally, Portulaca oleracea Linn. is used for treating abscesses, dysentery and liver diseases. In addition, recent studies have reported its efficacy as an analgesic, as neuroprotective, anti-inflammatory, bronchodilatory, and anticancer agent, besides antioxidant, wound healing and other important pharmacological actions. AIMS AND OBJECTIVES: For curing liver diseases, Chinese use juice from the fresh leaves of Portulaca oleracea Linn. Hence, to prove this claim, an in-vivo hepatoprotective study of extracts from Portulaca oleracea Linn. against carbon tetrachloride hepatotoxic rats was carried out. METHODS: The in-vitro antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and hepatoprotective activity of extracts of Portulaca oleracea Linn. was assessed against the carbon tetrachloride-induced toxicity rat model. RESULTS: The extracts of Portulaca oleracea Linn produced concentration-dependent percentage inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and most significantly, by methanol extract. Among the extracts, methanol extract showed a significant decrease in Serum glutamic oxaloacetic transaminase (SGOT), Serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) levels and a significant increase in total protein (TP) levels against carbon tetrachloride-induced liver toxicity. CONCLUSION: From the results obtained, it was concluded that methanol extract of Portulaca oleracea Linn. possesses significant DPPH free radical scavenging and hepatoprotective potential.

Phytochemical screening and anti-oxidant activity of Sargassum wightii enhances the anti-bacterial activity against Pseudomonas aeruginosa.

In this study, the phytochemical, phenolic, flavonoid and bioactive compounds were successfully screened from crude extract of Sargassum wightii by LC-MS analysis after NIST interpretation. Bacterial growth inhibition study result was shown with 24 mm zone inhibition at 200 µg/mL concentration against P. aeruginosa. The increased phenolic content was much closed to gallic acid and the range was observed at 250 µg/mL concentration. In addition, flavonoid contents of the algae extract was indicated more significant with rutin at 200 µg/mL. In result, both the phenolic and flavonoid contents of the extract were more correlated with gallic acid and rutin. Further, the total anti-oxidant and DPPH radical scavenging activities were shown increased activity at 200 µg/mL concentrations. Furthermore, the excellent anti-bacterial alteration result was observed at 200 µg/mL concentration by minimum inhibition concentration. Therefore, the result was revealed that the marine algae Sargassum wightii has excellent phytochemical and anti-oxidant activities, and it has improved anti-bacterial activity against P. aeruginosa.

The Reproductive Toxicity Associated with Dodonaea viscosa, a Folk Medicinal Plant in Saudi Arabia.

Dodonaea viscosa is a medicinal plant which is being used to treat various diseases in humans. The available safety data suggest that the plant does not produce any side effects, or toxicity, in tested adult experimental animals. However, the influence of D. viscosa on fetus or embryonic development is largely not known. This study was conducted in order to find out the reproductive toxicity of D. viscosa in experimental animals. Zebrafish embryos were used as the in vivo developmental toxicity animal model. Methanolic crude extract, hexane, chloroform, and butanol fractions were prepared from the leaves of D. viscosa. Zebrafish embryos were exposed to serial dilution of crude extract and other fractions. The crude extract and hexane fraction induced higher level of toxicity in zebrafish embryos as compared to chloroform and butanol fractions. The phenol and flavonoid estimation revealed that crude leaves extract and hexane fractions had lower content of phenol and flavonoid. Two major compounds, phytol and methyl ester, of hexadecanoic acid were identified by gas chromatography and mass spectrophotometry (GC-MS) analysis. More detailed studies are needed to check the toxicity of D. viscosa in pregnant experimental animals; however, the results from this study have shown that D. viscosa possesses reproductive toxicity and its use and doses must be carefully monitored in pregnant patients.

Biosynthesized silver nanoparticles using Caulerpa taxifolia against A549 lung cancer cell line through cytotoxicity effect/morphological damage.

The Caulerpa taxifolia is excellent marine green algae, which produced enormous bioactive compounds with more biological activities. Also, it is an excellent source for synthesis of Ag NPs with increased bioactivity against various infections. In our study, the marine algae marine algae Caulerpa taxifolia mediated Ag NPs was synthesized effectively. The synthesized Ag NPs was characterized well using UV-spectrometer and X-ray powder diffraction (XRD) and confirmed as synthesized particle was Ag NPs. The available structure of the Ag NPs was morphologically identified by scanning electron microscope (SEM), and exact minimum size, polydispersive spherical shape of the entire Ag NPs structure was confirmed by Transmission electron microscope (TEM). Further, the anti-cancer efficiency of biosynthesized Ag NPs against A549 lung cancer cells was found at 40 µg/mL concentration by cytotoxicity experiment. In addition, the phase contrast images of the result were supported the Ag NPs, which damaged the A549 morphologically clearly. Finally, florescence microscopic images were effectively proved the anti-cancerous effect against A549 lung cancer cells due to the condensed morphology of increased death cells. All the confirmed in-vitro results were clearly stated that the Caulerpa taxifolia mediated Ag NPs has superior anti-cancer agent against A549 lung cancer cells.

Prevalence of Anxiety and Associated Factors among Pharmacy Students in Saudi Arabia: a Cross-Sectional Study.

METHODS: We used a cross-sectional design, and data collection was carried out over a period of two months from September 2018 to November 2018 using paper-based self-administered questionnaires. The General Anxiety Disorder-7 (GAD-7) scale was used to measure and classify anxiety among the study participants. RESULTS: The prevalence of anxiety among pharmacy students was 49% (83 students); 44 students (25.9%) had mild anxiety, while 24 (14.1%) students had moderate anxiety, and 15 (8.8%) severe anxiety. There were statistically significant differences in anxiety scores according to faculty type (p = 0.2) and nutritional status (p = 0.4). CONCLUSION: The findings of this study revealed that half of the pharmacy students suffered from anxiety incidence during their studies at the university. However, the majority of them are experiencing mild to moderate. This may have a significant impact on academic performance and necessitates special attention.

Prevalence and Use of Dietary Supplements Among Pharmacy Students in Saudi Arabia.

PURPOSE: Dietary supplements (DSs) are popular in many countries, and their use among individuals is increasing worldwide. Therefore, this study aimed to assess the prevalence and use of DSs among pharmacy students in King Saud University College of Pharmacy, Riyadh, Saudi Arabia. METHODS: This study used a cross-sectional design targeting male senior pharmacy students in their fourth and fifth years of Bachelor and Doctor of Pharmacy courses. The data were collected between August and October 2019 using paper-based questionnaires. RESULTS: A total of 46.8% of the students used DSs. Of all students surveyed, 19% used branded supplements whereas 9.7% used generic or local supplements and 12.3% used both generic and branded supplements. Furthermore, 8.2% students suffered from side effects, including 5.6% who suffered from nausea, vomiting, and diarrhea and 2.6% who suffered from headache, confusion, and disorientation. Approximately 24.6% of students used fiber DSs whereas 19% and 16.4% used DSs for protein and glucosamine/omega 3 fatty acids, respectively. CONCLUSION: The study findings indicated that the prevalence of DS use is increasing. However, approximately half of the respondents encourage the use of DSs only with a doctor's recommendation. Educating about the safe use of DSs is warranted.

Prevalence and Practice of Unused and Expired Medicine-A Community-Based Study among Saudi Adults in Riyadh, Saudi Arabia.

PURPOSE: The objective of the current study was to determine the prevalence and practice of unused and expired medicine among Saudi adults. Subjects and Methods. The study used cross-sectional web-based design to collect the data, over a period of 4 months among people who are living in Riyadh, Saudi Arabia. RESULTS: A total of 337 questionnaires were obtained during the study period. The majority of respondents were university graduates n = 251 (74.7%). The prevalence of unused medicine was n = 301 (89.3%). The most commonly used drugs were nonsteroidal anti-inflammatory drugs n = 272 (80.7%) and antibiotics n = 164 (48.7%). Of the participants, 186 (55.2%) checked the expiry date of the medicine before they purchase. Most of them n = 305 (90.5%) obtained medicine through prescription. About n = 219 (65%) of them keep the medicine until it expired; 48.1% throw away in the household garbage while only 18 (5.4%) of the respondents said to give it back to the medical store. CONCLUSION: The study revealed a high prevalence of unused medications among Saudi community. However, the disposable practice among the Saudi community was inadequate. Increasing awareness through education programs about proper disposable guidelines is necessary for controlling the medication wastage.

Chemotherapeutic Potential of Carthamus Oxycantha Root Extract as Antidiarrheal and In Vitro Antibacterial Activities.

Our research work was designed to investigate the curative and preventive effects of Carthamus oxycantha root extract against diarrhea and microorganisms. For the antibacterial experiment, the agar well diffusion method was used against standard bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeroginosa, and Salmonella typhi, while for the assessment of antidiarrheal activity, castor oil and the magnesium sulfate-induced diarrhea method was used on albino, laboratory-bred (BALB/c) mice at a dose rate of 200 and 400 mg/kg (body weight, b.w) orally. The methanol extract of C. oxycantha significantly (p < 0.001) decreased the frequency of defecation, and wet stools in a dose depended on the manner of after receiving magnesium sulfate (2 g/kg (b.w)) and castor oil (1.0 mL/mice). Furthermore, the extract of C. oxycantha showed concentration-dependent antimicrobial properties against S. aureus followed by S. typhi, E. coli, and P. aeroginosa bacterial strains, with inhibitions ranging from 10.5-15 mm. These findings show significant results that C. oxycantha is effective as an antidiarrheal and antibacterial agent. However, further works are needed to establish its mode of action.

Cell proliferation activity delineated by molecular docking of four new compounds isolated from the aerial parts of Suaeda monoica Forssk. ex. J.F. Gmel.

Using different chromatographic methods, four new compounds were isolated from the aerial parts of Suaeda monoica (Chenopodiaceae) along with 2-hydroxy-1-naphthoic acid (SCM-3). The structures of the new compounds were established as 6'-hydroxy-10'-geranilanyl naphtha-1-oate (SMC-1), 4,4,8ß,10ß-Tetramethyl-9ß-isobutanyl decalin-13-ol-13-O-ß-D-xylopyranoside (SCM-2), 6'-(2-hydroxynaphthalen-3-yl) hexanoic acid (SCM-4) and 1'-(2-Methoxy-3-naphthyl)-4'-(2''-methylbenzoyl)-n-butane (SMC-5) by IR, EIMS and NMR (1 & 2D) analyses. All compounds (50 µg/mL) were tested for cell proliferative potential on cultured human liver cell HepG2 cells by MTT assay. The results revealed a marked cell proliferative potential of all compounds (1.42-1.48 fold) as compared to untreated control. The results of molecular docking and binding with specific proteins such as PTEN (Phosphatase and Tensin homolog) and p53 also justify the cell proliferative potential of the isolated compounds. Glide program with Schrodinger suit 2018 was used to evaluate the binding between SMC compounds and proteins (PTEN and p53). The binding affinity of all compounds was in order of 104-105 M-1 towards both PTEN and p53. All the SMC compounds have been found to bind at the active site of PTEN, thereby may prevent the binding of phosphatidylinositiol 3,4,5-triphosphate (PI3P). In the locked position, PTEN would not be able to hydrolyze PI3P and hence the PI3P regulated signaling pathway remains active. Similarly, SMC molecules were found to interact with the amino acid residues (Ser99, Thr170, Gly199, and Asp224) which are critically involved in the formation of tetrameric p53. The blockage of p53 to attain its active conformation thus may prevent the recruitment of p53 on DNA and hence may promote cell proliferation.

Role of LXR alpha in regulating expression of glucose transporter 4 in adipocytes - Investigation on improvement of health of diabetic patients.

BACKGROUND: The insulin-responsive glucose transporter 4 (GLUT4) plays prominent role in insulin-mediated facilitated glucose uptake into most of the cell types, majorly muscle, liver and adipose tissue. Impaired expression of GLUT4 has been linked to insulin resistance and diabetes. In adipocytes, excess lipids that are generated from liver and by de novo lipogenesis utilizing blood sugar, are stored. There are various nuclear factors, co-factors and signaling mechanisms that directly and indirectly regulate glucose transporter activity in adipocytes. Molecular mechanism behind the regulation of GLUT4 in adipocytes has not elucidated well. OBJECTIVE: Therefore, the present study focuses to explore the role of Liver X receptor- alpha (LXRα) on GLUT4 expression and the possible co-factors involved during in vitro adipogenesis and is assessed by modulating the activity of LXRα with specific agonist and antagonist ligands in 3T3L1 differentiated cells. RESULTS: The results demonstrate that SR 9238 (300nM), a strong inhibitor of LXRα, decreased the rate of adipogenesis through reduced lipid droplet formation in adipocytes without affecting the cell morphology. The FMOC-l-Leucine (FLL), a known partial ligand of PPARγ, enhanced the expression of LXRα. Thus, it can be concluded that LXRα has a significant role in adipocyte differentiation and FLL interaction promoted the transcription of LXRα, thereby promotes GLUT4 expression. The results in this study identified the role of LXRα in regulating the expression of GLUT4 through SRC1. CONCLUSION: The study is of much relevance in treatment of diabetes and also opens the possibility of identifying new drug molecules that target LXRα.

Antidiabetic, antioxidant, molecular docking and HPTLC analysis of miquelianin isolated from Euphorbia schimperi C. Presl.

The present study demonstrates the miquelianin or quercetin 3-O-glucuronide (compound 1) isolated from aerial parts of Euphorbia schimperi exhibited significant results for antioxidant and antidiabetic potential. The compound 1 along with kaempferol 3-O-glucuronide (compound 2) and quercetin 3-O-rhamnoside (compound 3) isolated from the same source were quantified by validated HPTLC method. Antioxidant activity was determined by chemical means in terms of ABTS radical cation and DPPH radical scavenging activity. Compound 1 showed significant scavenging activity in both ABTS and DPPH assays as compared to standard BHA. In ABTS method IC50 values of compound 1 and standard BHA is found to be 58.90 ±â€¯3.40 µg/mL and 28.70 ±â€¯5.20 µg/mL respectively while in DPPH assay IC50 values of Compound 1 and standard BHA is 47.20 ±â€¯4.90 µg/mL and 34.50 ±â€¯6.20 µg/mL respectively. Antidiabetic effect was studied through α-amylase and α-glucosidase inhibitory activity. The mechanistic approach through molecular modelling also support the strong binding sites of compound 1 which showed significant α-amylase and α-glucosidase inhibitory activities with IC50 values 128.34 ±â€¯12.30 and 89.20 ±â€¯9.20 µg/mL respectively as compared to acarbose 64.20 ±â€¯5.60 and 52.40 ±â€¯4.60 µg/mL respectively. The results of validated RP-HPTLC analyses revealed the concentration of compound 1 found to be 16.39 µg/mg and for compound 2 and compound 3 as 3.92 and 14.98 µg/mg of dried extract, respectively.

Thermodynamic solubility and solvation behavior of ferulic acid in different (PEG-400 + water) binary solvent mixtures.

This work was carried out to determine solubility, solution thermodynamics, solvation behavior, and molecular interactions of a natural compound ferulic acid (FLA) in different '[polyethylene glycol-400 (PEG-400) + water]' binary solvent mixtures at 'T = 298.2 K to 318.2 K' and 'p = 0.1 MPa.' The mole fraction solubilities (xe) of FLA were determined by liquid chromatographic technique using a static equilibrium technique. The obtained solubility data of FLA were regressed using 'Van't Hoff, Apelblat, Yalkowsky-Roseman and Jouyban-Acree models.' The solubility of FLA (expressed in mole fraction) was enhanced with elevation in absolute temperature in each 'PEG-400 + water' binary solvent mixture evaluated. The maximum xe values of FLA were recorded in neat PEG-400 (1.94 × 10-1) at 'T = 318.2 K.' While, the minimum one was obtained in neat water (4.90 × 10-5) at 'T = 298.2 K.' The molecular interactions between FLA-PEG-400 and FLA-water were obtained by determination of activity coefficients of FLA in different 'PEG-400 + water' binary solvent mixtures. The physical data of activity coefficients recorded in this work suggested strong molecular interactions in FLA-PEG-400 in comparison with FLA-water. 'Apparent thermodynamic analysis' suggested an 'endothermic and entropy-driven dissolution' of FLA in each 'PEG-400 + water' binary solvent mixture investigated.

Betulinic acid lowers lipid accumulation in adipocytes through enhanced NCoA1-PPARγ interaction.

BACKGROUND: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. METHODS: Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. RESULTS: Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. CONCLUSION: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation.

The influence of variations of furanosesquiterpenoids content of commercial samples of myrrh on their biological properties.

Myrrh is an oleo-gum-resin produced in the stem of Commiphora myrrha (Burseraceae) and used for centuries for different medicinal purposes. The present work was designed to evaluate the cytotoxic and antioxidant properties of seventeen myrrh samples (S1-S17) obtained from different retail markets of Saudi Arabia and Yemen regions, along with two furanosesquiterpenoids (CM-1 and CM-2). The cytotoxicity assay was carried out on HepG2, MCF-7 and HUVEC cell lines. S2, S5, S10, S12, CM-1, CM-2 exhibited significant cytotoxicity against HepG2/MCF-7 cell lines [IC50 (µg/mL): 13.8/10, 14/10, 14.5/11.3, 18/13.2, 9.5/12.5, 10/15.8, respectively) compare to vinblastin (IC50 (µg/mL): 2/2.5) whereas the remaining samples were found as mild active or inactive. The antioxidant properties of the samples were tested by ß-carotene-bleaching and DPPH free radical scavenging methods where the samples S8 (1000 µg/mL) exhibited the highest ß-carotene bleaching (76.2%) and free radical scavenging activity (79.8%). The HPTLC analysis was performed on NP-HPTLC plate using toluene, chloroform and glacial acetic acid as mobile phase in ratio of 7:2.9:0.1 (V/V/V). The validated HPTLC method furnished sharp, intense and compact peaks of CM-1 and CM-2 at Rf = 0.39 and 0.44, respectively. The highest/lowest content of CM-1 and CM-2 were found in S12/S5 and S5/S17, respectively. The molecular docking studies of CM-1 and CM-2 with human DNA topoisomerase IIα have shown that both the compounds were bound the active sites of the respective enzymes. Molecular dynamics simulation studies further confirmed that the interactions of CM-1 and CM-2 with topoisomerase were stable in nature. This study will help us in selection of appropriate myrrh sample for the greater benefits of the population in the Middle East region.

Anticancer activity and concurrent analysis of ursolic acid, ß-sitosterol and lupeol in three different Hibiscus species (aerial parts) by validated HPTLC method.

The genus Hibiscus contains about 275 species of flowering plants widely grown in the tropics and sub-tropics. The available literature revealed that several Hibiscus species exhibited excellent anticancer activity against several cancer cells like lung, breast, and liver. This motivated the authors to explore the anticancer property of other Hibiscus species (Hibiscus calyphyllus, H. deflersii and H. micranthus) along with development of a validated HPTLC method for the concurrent analysis of three anticancer biomarkers (ursolic acid, ß-sitosterol and lupeol) in different Hibiscus species. The anticancer activity of various fractions (petroleum ether, toluene, dichloromethane, ethyl acetate and n-butanol) of all the Hibiscus species (aerial parts) were evaluated in vitro against HepG2 and MCF-7 cell lines using MTT assay. The HPTLC analysis was carried out using chloroform and methanol as mobile phase (97:3; v/v) on 20 × 10 cm glass-backed silica gel 60F254 plates and analyzed different phytoconstituents present in all fractions at λ = 575 nm wavelength. Of the tested fractions of H. calyphyllus, H. deflersii and H. micranthus, HdP (H. deflersii petroleum ether fraction) exhibited the most potent cytotoxic effect on HepG2 and MCF-7 (IC50: 14.4 and 11.1 µg/mL, respectively) cell lines. Using the developed HPTLC method a compact and intense peak of ursolic acid, ß-sitosterol and lupeol were obtained at Rf = 0.22, 0.39 and 0.51, respectively. The LOD/LOQ (ng) for ursolic acid, ß-sitosterol and lupeol were found as 42.30/128.20, 13.20/40.01 and 31.57/95.68, respectively in the linearity range 100-1200 ng/spot. The obtained result showed maximum presence of ursolic acid, ß-sitosterol and lupeol (5.50, 11.85 and 7.47 µg/mg, respectively) in HdP which also supported its strong anticancer effect. Our data suggest that H. deflersii petroleum ether fraction (HdP) can be further subjected to the isolation of active cytotoxic phytoconstituents and establishment of their mechanism of action. The maiden developed HPTLC method for concurrent analysis of anticancer biomarkers may be further employed in the in process quality control of herbal formulation containing the said biomarkers.

A comprehensive review on Brigatinib - A wonder drug for targeted cancer therapy in non-small cell lung cancer.

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90 mg of brigatinib for 7 days and then 180 mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.

Concurrent analysis of bioactive triterpenes oleanolic acid and ß-amyrin in antioxidant active fractions of Hibiscus calyphyllus, Hibiscus deflersii and Hibiscus micranthus grown in Saudi Arabia by applying validated HPTLC method.

In this study, we developed a validated HPTLC method for concurrent analysis of two natural antioxidant triterpenes, oleanolic acid (OA) and ß-amyrin (BA) in the biologically active fractions (petroleum ether, toluene, chloroform, ethyl acetate and n-butanol) of aerial parts of three Hibiscus species (H. calyphyllus, H. deflersii and H. micranthus). The chromatography was conducted on normal HPTLC (ready to use glass-plate coated with silica gel 60 F254) plate with chloroform and methanol (97:3, V/V) used as mobile phase. The derivatization of the developed plate was done with p-anisaldehyde and scanned at λmax = 575 nm. Well resolved and intense peaks of OA and BA were obtained at Rf = 0.36 and 0.57, respectively. The linear regression equation/correlation coefficient (r2) for OA and BA were Y = 6.65x + 553.35/0.994 and Y = 9.177x + 637.23/0.998, respectively in the linearity range of 100-1200 ng/spot indicated good linear relationship. The low values of %RSD for intra-day/inter-day precision of OA (1.45-1.61/1.38-1.59) and BA (1.52-1.57/1.50-1.53) suggested that the method was precise. The recovery/RSD (%) values for OA and BA were found to be 99.21-99.62/1.39-1.95 and 98.75-99.70/1.56-1.80, respectively assures the reasonably good accuracy of the proposed method. Fifteen samples were analyzed to check the content of OA and BA by using the developed HPTLC methods. The content of OA in different samples were found to be 3.87 (HmP) > 1.212 (HcP) > 0.673 (HdC) > 0.493 (HdP) > 0.168 (HdE) > 0.059 (HcC) > 0.015 (HcE) > 0.008 (HmT) µg/mg of the dried weight of extract. However the content of BA was found as: 2.293 (HmP) > 1.852 (HdT) > 0.345 (HdC) > 0.172 (HmT) > 0.041 (HdE) > 0.008 (HcC) µg/mg of the dried weight of extract. Some Hibiscus species fractions exhibited good antioxidant potential like: HcE (IC50 = 17.6 ±â€¯1.8) > HdB (IC50 = 32.16 ±â€¯0.9) > HmP (IC50 = 80.4 ±â€¯4.5) > HmT (IC50 = 99.7 ±â€¯8.2) when compared with ascorbic acid (IC50 = 14.2 ±â€¯0.5), while other fractions exhibited only mild antioxidant capability. The developed HPTLC method can be further exploited for analysis of these markers in the quality assessment of raw material as well as herbal formulations available in the market.