Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

Cellular and Non-cellular Antioxidant Properties of Vitamin E-Loaded Metallic-Quercetin/Polycaprolactone Nanoparticles for the Treatment of Melanogenesis.

Inhibition of melanogenesis by quercetin and vitamin E is extensively reported in the literature, independently, with limitations in antioxidant potential owing to less permeation, solubility, decreased bioavailability, and reduced stability. Thus, the aim of the present study was to synthesize a novel complex of metal ions (copper and zinc) with quercetin to enhance antioxidant properties which were confirmed by docking studies. Polycaprolactone-based nanoparticles of the synthesized complex (PCL-NPs, Q-PCL-NPs, Zn-Q-PCL-NPs, Cu-Q-PCL-NPs) were made later loaded with vitamin E which made the study more interesting in enhancing antioxidant profile. Nanoparticles were characterized for zeta size, charge, and polydispersity index, while physiochemical analysis of nanoparticles was strengthened by FTIR. Cu-Q-PCL-NPs-E showed maximum in vitro release of vitamin E, i.e., 80 ± 0.54%. Non-cellular antioxidant effect by 2,2-diphenyl-1-picrylhydrazyl was observed at 93 ± 0.23% in Cu-Q-PCL-NPs-E which was twofold as compared to Zn-Q-PCL-NPs-E. Michigan Cancer Foundation-7 (MCF-7) cancer cell lines were used to investigate the anticancer and cellular antioxidant profile of loaded and unloaded nanoparticles. Results revealed reactive oxygen species activity of 90 ± 0.32% with the addition of 89 ± 0.64% of its anticancer behavior shown by Cu-Q-PCL-NPs-E after 6 and 24h. Similarly, 80 ± 0.53% inhibition of melanocyte cells and 95 ± 0.54% increase of keratinocyte cells were also shown by Cu-Q-PCL-NPs-E that confirmed the tyrosinase enzyme inhibitory effect. Conclusively, the use of zinc and copper complex in unloaded and vitamin E-loaded nanoparticles can provide enhanced antioxidant properties with inhibition of melanin, which can be used for treating diseases of melanogenesis.

The genus Cassia L.: Ethnopharmacological and phytochemical overview.

Nature gifts medicinal plants with the untapped and boundless treasure of active chemical constituents with significant therapeutic potential that makes these plants a beneficial source in the development of phytomedicines. Genus Cassia, with approximately 500 species, is a large group of flowering plants in the family Fabaceae. Cassia species are widely distributed throughout different regions mainly tropical Asia, North America, and East Africa. In the folk medicinal history, these plants are used as laxative and purgative agents. In the Ayurveda system of medicine, they are used to cure headache and fever. Cassia plants exhibit pharmacological activities at large scales such as antimicrobial, anticancer, antiinflammatory, antioxidant, hypoglycemic, hyperglycemic, antimutagenic, and antivirals. The phytochemical investigations of genus Cassia demonstrate the presence of more than 200 chemical compounds, including piperidine alkaloids, anthracene derivatives (anthraquinones), flavonoids, pentacyclic triterpenoids, sterols, phenylpropanoids, and γ-naphthopyrones. The literature illustrated anthraquinones and flavonoids as major secondary metabolites from this genus. However, some Cassia plants, with rich contents of anthraquinones, still show toxicology properties. As Cassia plants are used extensively in the herbal system of medicine, but only senna dosage forms have achieved the status of the pharmaceutical market as standard laxative agents. In conclusion, further investigations on isolating newer biologically active constituents, unknown underlying mechanisms, toxicology profiles, and clinical studies of Cassia species are needed to be explored. This review article specifies the systematic breach existing between the current scientific knowledge and the fundamentals for the marketization of genus Cassia products.

Pharmacological support to anti-arthritic prospective of physostigmine: a new approach.

Rheumatoid arthritis (RA) is a slowly progressing inflammatory autoimmune disease. Several features are involved in the RA pathogenesis in addition to environmental and genetic factors. Previously it has been reported that acetyl cholinesterase (AChE) activity is enhanced in old age and may contribute in the progression of RA. The current experimental work was projected to assess the activity of physostigmine (a cholinesterase inhibitor) for treatment of RA. In vitro and in vivo approaches were used for such evaluation. However, enzyme linked immunosorbent assays (ELISA) was performed to determine the concentrations of Prostaglandins E2 (PGE2) and tumor necrosis factor-α in arthritic rats after treatment with physostigmine. Moreover, anti-oxidant assays were employed to calculate the level of super oxide dismutase (SOD) and catalase peroxidase (CAT) in tissue of treated animals. The results claimed the dose dependent protective and stabilizing effect of physostigmine on denaturation of albumin (egg and bovine serum) protein and human red blood cell membrane, respectively, through in vitro studies. Furthermore, the physostigmine (10 and 20 mg/kg) significantly (p < 0.001) reduced the swelling of paw after induction of arthritis with formaldehyde or complete Freund's adjuvant (CFA) as compared to arthritic control animals. Moreover, significant (p < 0.001) reduction in the levels of inflammatory markers (PGE2 and TNF-α) at doses of 10 and 20 mg/kg of physostigmine has been observed in ELISA test. Likewise, there was a prominent rise in levels of SOD and CAT in animals treated with physostigmine. These findings pharmacologically conclude the anti-arthritic effect of physostigmine.

Evaluation of the cytotoxic potential of a new pentacyclic triterpene from Rhododendron arboreum stem bark.

CONTEXT: Traditionally, Rhododendron arboreum Sm. (Ericaceae) is a very important medicinal plant having oxytocic, estrogenic, anti-inflammatory, analgesic and hepatoprotective activities; it also inhibits the prostaglandin synthetase. OBJECTIVES: This study determines the cytotoxic potential of 15-oxoursolic acid isolated from R. arboreum against selected human cancer cell lines. MATERIALS AND METHODS: Extraction from stem bark (5 kg) of R. arboreum was performed with methanol, which was successively partitioned into hexane, dichloromethane and ethyl acetate fractions, respectively. The new antitumor agent [15-oxoursolic acid (1)] was isolated from ethyl acetate fraction through column chromatography. Structure elucidation of new compound was performed through extensive spectroscopy i.e., IR, MS and 1D and 2D NMR. Cytotoxicity of isolated compound was determined at doses 5-100 µM for a period of 72 h on specified human cancer cell lines [renal cell carcinoma (A498), non-small cell lung (NCI-H226), squamous cell carcinoma (H157) and human ovarian carcinoma (MDR-2780AD)]. RESULTS: Structure of isolated compound was characterized as 15-oxoursolic acid on the basis of various extensive spectroscopic techniques. 15-Oxoursolic acid revealed considerable anticancer activity with IC50 values of 2.3 ± 0.1 µM, 4.9 ± 0.2 µM, 9.2 ± 0.2 µM and 10.3 ± 0.1 µM against MDR 2780AD, Hep G2, H157 and NCI-H226, respectively, while in the case of A498, the activity was good (IC50 32.8 ± 1.2 µM). CONCLUSIONS: This study highlighted the potential of 15-oxoursolic acid to be further explored as a new lead compound for cancer chemotherapy.

EVALUATION OF HEPATOPROTECTIVE ACTIVITY OF MELILOTUS OFFICINALIS L. AGAINST PARACETAMOL AND CARBON TETRACHLORIDE INDUCED HEPATIC INJURY IN MICE.

Hepatic diseases are becoming common day by day and pose serious health threats to the life of humans. In order to treat these diseases, the attention of man is diverting towards herbal drugs, which are much safer and cost effective than synthetic drugs. The aim of present study was to investigate hepatoprotective activity of methanolic extract of Melilomus officinalis against paracetamol and carbon tetrachloride induced hepatic damage. Melilotus officinalis at selected oral doses of 50 mg/kg and 100 mg/kg showed significant hepatoprotective effects by decreasing the levels of serum marker enzymes such as total bilirubin, SGOT, SGPT, ALP, albumin and total protein, when compared with standard drug (silymarin) and negative control. Similarly, histopathological studies also supported biochemical estimations. It was concluded that extract of Melilotus officinali has strong hepatoprotective activity against paracetamol and carbon tetrachloride induced hepatotoxicity, which might be due to free radical scavenging mechanisms exhibited by flavonoids and phenolics, thus affirming its traditional therapeutic role in liver injury.

Storage Stability of Kinnow Fruit (Citrus reticulata) as Affected by CMC and Guar Gum-Based Silver Nanoparticle Coatings.

The influence of carboxy methyl cellulose (CMC) and guargum-based coatings containing silver nanoparticles was studied on the postharvest storage stability of the kinnow mandarin (Citrus reticulata cv. Blanco) for a period of 120 days (85%-90% relative humidity) at 4 °C and 10 °C. Physicochemical and microbiological qualities were monitored after every 15 days of storage. Overall results revealed an increase in total soluble solid (TSS), total sugars, reducing sugars and weight loss but this increase was comparatively less significant in coated fruits stored at 4 °C. Ascorbic acid, total phenolics, and antioxidant activity was significantly enhanced in coated fruits stored at 4 °C. Titratable acidity significantly decreased during storage except for coated kinnow stored at 4 °C. In control samples stored at 10 °C, high intensity of fruit rotting and no chilling injury was observed. Total aerobic psychrotrophic bacteria and yeast and molds were noticed in all treatments during storage but the growth was not significant in coated fruits at 4 °C. Kinnow fruit can be kept in good quality after coating for four months at 4 °C and for 2 months at 10 °C.

Preliminary phytochemical screening, antimicrobial and antioxidant activities of Euphorbia milli.

Euphorbia milii is a Pakistani herb used for various infectious diseases. In this study we have carried out phytochemical, antibacterial and antioxidant investigation of different extracts/fractions. Phytochemical studies showed the presence of cardiac glycosides, steroids/phytosterols, anthocyanin, proteins, terpenoids, flavonoids and tannins. Susceptibility testing by well diffusion assay of its chloroform and methanol fractions revealed good antimicrobial activity against Klebsiella pneumonia and Staph epidermis. Ethyl acetate fraction of roots also exhibited considerable antimicrobial activity against most of tested pathogens. Various fractions (Hexane, chloroform, methanol and water) of E. milii were screen for their antioxidant potential using DPPH radical scavenging assay at different concentrations among these, chloroform fraction exhibited good scavenging activity. The IR spectroscopy of the various extracts/fractions indicated the presence of OH, saturated CH stretching, C=C, C=O, NO2, C-N, Ar-O, C-O- and R-O-Stretching respectively. The findings provide helpful evidence for the use of E. milii in traditional medicines.

Nutritionally rich biochemical profile in essential oil of various Mentha species and their antimicrobial activities.

The Mentha species of family Lamiaceae are famous for their flavor and are commercially used in many food products worldwide. They are widely used to cure digestive problems as well as a natural source of antioxidants and antimicrobials. In this report, the essential oils (EOs) of five Mentha species, namely Mentha citrata, Mentha x piperita, Mentha pulegium, Mentha spicata, and Mentha suaveolens were extracted and their chemical diversity was investigated through gas chromatography-mass spectroscopy (GC-MS). The differential doses (5, 10, and 15 µl) of EOs were tested for antimicrobial potential against two gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), five gram-negative bacteria (Escherichia coli, Pseudomonas aeroginosa, Salmonella typhi, Proteus mirabilis and Klebsiella pneumoniae) and a fungal strain (Candida albicans). The GC-MS results revealed the major components in the EOs were Carvone, Linalool, Hotrienol, Menthol, Isopulegone, Furanone, Piperitone, and Thymol. Moreover, the higher dose (15 µl) of EOs of M. citrata inhibited the growth of S. typhi and C. albicans (35.8 ± 2.4 and 35.2 ± 2.5 mm), M. x piperita inhibited E. coli, B. subtilis, and C. albicans (28.5 ± 3.5, 26.1 ± 2.1, and 25.4 ± 1.1 mm), M. pulegium inhibited K. pneumoniae, B. subtilis, and C. albicans (26.8 ± 1.8, 24.2 ± 2.2, and 25.3 ± 0.9 mm), M. spicata significantly inhibited S. typhi and B. subtilis (35.7 ± 2.7 and 36.3 ± 2.1 mm), and M. suaveolens inhibited K. pneumoniae, C. albicans, and S. typhi (30.8 ± 1.9, 26.9 ± 1.1, and 20.1 ± 0.8 mm) respectively. This study concluded that the EOs of M. citrata was effective against S. typhi and C. albicans. The M. x piperita exhibited strong activities against E. coli, B. subtilis, and C. albicans. Furthermore, the M. pulegium strongly inhibited the growth of K. pneumoniae and C. albicans. The EO of M. spicata was more potent against S. typhi and B. subtilis, while the M. suaveolens was comparatively more effective against S. typhi, K. pneumoniae, and C. albicans. These EOs offer a natural source of antimicrobial agents with high commercial values and social acceptance and could be scale up by food and pharmaceutical industries to control pathogenic diseases.

Correlation between Chemical Composition of Curcuma domestica and Curcuma xanthorrhiza and Their Antioxidant Effect on Human Low-Density Lipoprotein Oxidation.

The antioxidant activity of the curcuminoids of Curcuma domestica L. and C. xanthorrhiza Roxb. and eight compounds which are prevalent constituents of their rhizome oils were investigated in an effort to correlate human low-density lipoprotein (LDL) antioxidant activity with the effect of the herbs and their components. The antioxidant activity was examined using thiobarbituric acid reactive substances (TBARSs) assay with human LDL as the oxidation substrate. The methanol extracts and rhizome oils of C. xanthorrhiza and C. domestica showed strong inhibitory activity on copper-mediated oxidation of LDL. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin, isolated from the methanol extracts of both plants, exhibited stronger activity than probucol (IC(50) value 0.57 µmol/L) as reference, with IC(50) values ranging from 0.15 to 0.33 µmol/L. Xanthorrhizol, the most abundant component (31.9%) of the oil of C. xanthorrhiza, showed relatively strong activity with an IC(50) value of 1.93 µmol/L. The major components of C. domestica, ar-turmerone (45.8%) and zerumbone (3.5%), exhibited IC(50) values of 10.18 and 24.90 µmol/L, respectively. The high levels of curcuminoids in the methanol extracts and xanthorrhizol, ar-turmerone and zerumbone in the oils, and in combination with the minor components were responsible for the high LDL antioxidant activity of the herbs.

Brand Love: Role of Online Customer Experience, Value Co-creation, and Relationship Quality.

Customer experience is a source of retailers' long-term competitive advantage. This study has examined the relationship between online customer experience and brand love through the mechanism of relationship quality in the context of online shopping in Pakistan. The moderating effect of value co-creation on the relationship of online customer experience with relationship quality and brand love has also been examined. Data were collected from a purposive sampling of 189 online customers in an online survey. Results showed that online customer experience significantly impacts customer relationship quality, which leads to brand love. The relationship between online customer experience and relationship quality is found more robust at high levels of value co-creation. However, we observed a significant negative moderating effect of value co-creation on the direct relationship between online customer experience and brand love. It suggests that including customers in the value co-creation process and affording them a pleasurable online shopping experience may be an excellent way to enhance customer relationship quality and brand love. Theoretical and practical implications of these findings are discussed.

Online Customer Experience Leads to Loyalty via Customer Engagement: Moderating Role of Value Co-creation.

With the increasing growth of online shopping, businesses are intertwining to establish new shopping antecedents. Customer experience has steadily become the most important source of retailers' long-term competitive advantage via difference. To preserve long-term and sustained consumer loyalty, retailers must continually improve the customer experiences. This study presents a framework for online retailing in a digital environment called the Online Customer Experience-Engagement Context model in the presence of value co-creation (VCC). Data was gathered from 189 people who purchased products online. For additional analysis, testing the hypothesis, and model construction, SPSS 26 and Smart-PLS were used. The data was then evaluated further using descriptive statistics, path analysis, measurement, and structural model. The findings show that the online customer experience (measured as shopping environment, shopping procedure, staff service experience, and product experience) substantially influenced customer engagement, which improved customer loyalty. The VCC strengthened the link between online customer experience and customer engagement. It suggests that including consumers in co-creating a delightful online customer experience from time to time may be a valuable strategy for online retailers to increase customer engagement and loyalty. To create an overarching outcome, information integration theory (IIT), multi-attribute utility theory (MAUT), and the attitude-behavior-context theory (ABC) theories are converged to explain the proposed model in the study.

Adequacy of Pain Control in Patients With Advanced Cancer in Pakistan.

PURPOSE:: Pain is highly prevalent in advanced cancer and requires aggressive management. However, pain management in cancer is minimally investigated in Pakistan. This cross-sectional study explores the adequacy of pain management in patients with advanced stage cancer in Pakistan. METHOD:: From January 2017 to May 2017, a cross-sectional study was conducted at Mayo Hospital, Lahore, Pakistan. A total of 218 patients with cancers were interviewed, and 136 patients with pain ≥5 on a Numerical Rating Scale for pain were included in the study. Demographic of patients and clinical characteristics of tumors were also evaluated. RESULTS:: Only about one-third of the patients with advanced cancer reported adequate pain management. Chi-square test, χ2 (1, n = 136) = 33.038, P < .05, indicated that pain scores were inversely associated with pain control; inadequate pain control was observed in patients with higher pain score and vice versa. Of the 55.88% of patients who were prescribed morphine, only 6 patients were compliant with treatment recommendations. Most patients were prescribed nonopioid medications and tramadol and codeine, which are weak opioid medications. CONCLUSION:: The rate of undertreatment of cancer pain in Pakistan is alarming. Inadequate clinicians' training, patients' and caregivers' beliefs, lack of availability of opioid medications, and socioeconomic factors are some of the barriers to effective pain control. A multidisciplinary team approach is necessary to follow the World Health Organization pain ladder guidelines for the treatment of cancer pain.

Development and in vitro evaluation of (ß-cyclodextrin-g-methacrylic acid)/Na+-montmorillonite nanocomposite hydrogels for controlled delivery of lovastatin.

Background: Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage.  It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. Purpose: The objective of this study was to prepare and optimize nontoxic, biocompatible ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. Methods: ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using  ß-CD  as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Results: Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R2 and "n" value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. Conclusion: A novel pH responsive crosslinked network containing ß-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.

Frequency and correlates of symptoms of anxiety and depression among young caregivers of cancer patients: a pilot study.

OBJECTIVES: To determine the frequency of symptoms of anxiety and depression among the young caregivers of family members with cancer and their correlation with role of gender, age and socio-economic status. RESULTS: A total of 87.8% of caregivers were between 11 and 16 years of age, with 94.6% reported having support from another caregiver. At least 95% of caregivers reported symptoms of anxiety with a higher predisposition among females. Around 73% of caregivers had low monthly incomes followed by (22.9%) middle and (4.1%) high monthly incomes. Care givers belonging to low income groups were more likely to report anxiety and depressive symptoms (70%). Young adults 17-18 years of age reported fewer symptoms of anxiety (10.9%) than their younger counterparts. Reported symptoms of anxiety and depression decreased when the number of care givers increased-2 (67.5%), 3 (16.2%), 4 (5.4%). Increased hospital stay was associated with increased frequency of symptoms, but not beyond 5 weeks.