Fabrication, organoleptic evaluation and in vitro characterization of cream loaded with Carica papaya seed extract.

OBJECTIVE: The current study aimed to provide preliminary insights into potential biopharmaceutical applications of Carica papaya seed extract by evaluating its phytochemical and biological profiles. Furthermore, the study aimed to develop a stable oil-in-water (O/W) emulsion for the effective delivery of antioxidant-rich biologicals for cosmetic purposes. METHODS: The hydroethanolic (ethanol 80%: 20% water) extract of C. papaya seeds was prepared via maceration technique. The chemical composition was carried out through preliminary phytochemical screening and estimation of total phenolic contents (TPC) and total flavonoid contents (TFC). The biological profile of the extract was explored using various in-vitro antioxidant methods. The homogenization procedure was used to create a cream of O/W and various tests were applied to assess the stability of the emulsion. By keeping the emulsion at different storage conditions (8 ± 0.5°C, 25 ± 0.5°C, 40 ± 0.5°C, and 40 ± 0.5°C ± 75% relative humidity [RH]) for a period of 28 days), the physical stability parameters of the emulsion, including pH, viscosity, centrifugation, phase separation, and conductivity, as well as rheological parameters and organoleptic parameters (odor, color, liquefaction, and creaming), were assessed. RESULTS: The preliminary phytochemical screening assay revealed the presence of various plant secondary metabolites including alkaloids, phenolics, flavonoids, tannins, saponins, and quinones. The extract was found to be rich in TPC and TFC. The in vitro antioxidant study gave maximum activity in the DPPH method. The plant extract containing cosmetic cream exhibited remarkable stability during the entire research. Data gathered indicated that no phase separation or liquefaction was seen after the experimental period. Throughout the experimental period, a small variation in the pH and conductivity values of the base and formulation was seen. CONCLUSION: The findings suggest that the seed extract of C. papaya is a rich source of polyphenols with antioxidant potential and can be a promising alternative for the treatment of various ailments. The stability of emulsion paves the way for its utilization as a carrier for the delivery of 3% C. papaya seed extract and applications in cosmetics products.

Antioxidant, carbonic anhydrase inhibition and diuretic activity of Leptadenia pyrotechnica Forssk. Decne.

Background: Leptadenia pyrotechnica Forssk. Decne is a member of family Apocynaceae and locally known as 'Khipp'. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of L. pyrotechnica in nephrolithiasis, kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of L. pyrotechnica as diuretic. Methods: The 70 % methanolic L. pyrotechnica (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition. Results: Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10-300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways. Conclusion: L. pyrotechnica contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways.

Anti-inflammatory, anti-nociceptive and anti-pyretic activities of Cenchrus ciliaris L.

ETHNOPHARMACOLOGICAL RELEVANCE: Cenchrus ciliaris L. belongs to the family Poaceae and is found all over the world. It is native to the Cholistan desert of Pakistan where it is locally known as 'Dhaman'. Owing to high nutritional value, C. ciliaris is used as fodder while seeds are used for bread making which are consumed by locals. It also possesses medicinal value and is extensively employed to treat pain, inflammation, urinary tract infection, and tumors. AIM OF STUDY: Studies on the pharmacological activities of C. ciliaris are scarce in spite of its several traditional uses. To the best of our knowledge, no comprehensive study has been conducted on anti-inflammatory, analgesic and anti-pyretic activity of C. ciliaris until now. Here we employed an integrative phytochemical and in - vivo framework to evaluate the potential biological activities of C. ciliaris against inflammation, nociception and pyrexia experimentally induced in rodents. MATERIAL AND METHODS: C. ciliaris was collected from the desert of Cholistan, Bahawalpur, Pakistan. Phytochemical profiling of C. ciliaris was done by employing GC-MS analysis. Anti-inflammatory activity of plant extract was initially determined by various in - vitro assays including albumin denaturation assay and RBC membrane stabilization assays. Finally, rodents were utilized to evaluate in - vivo anti-inflammatory, antipyretic and anti-nociceptive activities. RESULTS: Our data revealed the presence of 67 phytochemicals in methanolic extract of C. ciliaris. The methanolic extract of C. ciliaris provided RBC membrane stabilization by 65.89 ± 0.32% and protection against albumin denaturation by 71.91 ± 3.42% at 1 mg/ml concentration. In in - vivo acute inflammatory models, C. ciliaris exhibited 70.33 ± 1.03, 62.09 ± 8.98, 70.24 ± 0.95% anti-inflammatory activity at concentration of 300 mg/ml against carrageenan, histamine and serotonin induced inflammation. In CFA induced arthritis, inhibition of inflammation was found to be 48.85 ± 5.11% at 300 mg/ml dose after 28 days of treatment. In anti-nociceptive assays C. ciliaris exhibited significant analgesic activity in both peripheral and centrally mediated pain. The C. ciliaris also reduced the temperature by 75.26 ± 1.41% in yeast induced pyrexia. CONCLUSION: C. ciliaris exhibited anti-inflammatory effect against acute and chronic inflammation. It also showed significant anti-nociceptive and anti-pyretic activity which endorses its traditional use in the management of pain and inflammatory disorders.

Assessment of the dibenzothiophene desulfurization potential of indigenously isolated bacterial consortium IQMJ-5: a different approach to safeguard the environment.

Biodesulfurization is emerging as a valuable technology for the desulfurization of dibenzothiophene (DBT) and its alkylated substitutes, which are otherwise regarded as refractory to other physical and chemical desulfurizing techniques. The inability of the currently identified pure cultures and artificial microbial consortia due to lower desulfurization rate and product inhibition issues has compelled the researcher to look for an alternative solution. Thus, in the present study, an indigenously isolated microbial consortium was employed to tackle the desulfurization issue. Herein, we isolated several kinds of DBT desulfurizing natural microbial consortia from hydrocarbon-contaminated soil samples by conventional enrichment technique. The most effective desulfurizing microbial consortium was sequenced through illumine sequencing technique. Finally, the effect of the products of the desulfurizing pathway (such as 2-hydroxybiphenyl (2-HBP) and sulfate (SO4-2) was evaluated on the growth and desulfurization capability of the isolated consortium. The outcomes of Gibb's assay analysis showed that six isolates followed the "4S" pathway and converted DBT to 2-HBP. Among the isolates, I5 showed maximum growth rate (1.078 g/L dry cell weight) and desulfurization activity (about 77% as indicated by HPLC analysis) and was considered for further in-depth experimentation. The analysis of 16S rRNA by high-throughput sequencing approach of the I5 isolate revealed five types of bacterial phyla including Proteobacteria, Bacteroidetes, Firmicutes, Patescibacteria, and Actinobacteria (in order of abundance). The isolate showed significant tolerance to the inhibitory effect of both 2-HBP and SO4-2 and maintained growth in the presence of even about 1.0 mM initial concentration of both products. This clearly suggests that the isolate can be an efficient candidate for future in-depth desulfurization studies of coal and other fossil fuels.

Polymeric Nanogel for Oral Delivery of the Chemotherapeutic Agent: Fabrication and Evaluation Alongside Toxicological Studies and Histopathological Examination.

Nanogel has attracted considerable attention as one of the most versatile drug delivery systems, especially for site-specific and/or time-controlled delivery of the chemotherapeutic agent. The main objective of this study was to prepare the polymeric nanogel characterized by Fourier transform infrared spectroscopy, x-ray diffraction, thermogravimetric analysis, differential scanning, and oral acute toxicity. Free radical polymerization was done for the fabrication of polymeric nanogel. Fourier transform infrared spectroscopy was used to confirm the successful free radical polymerization. Various techniques such as x-ray diffraction, differential scanning calorimetric, and thermogravimetric analysis measurement were used to investigate the thermal behavior and crystallinity of developed nanogel. Parameters such as swelling, drug loading, and in vitro drug release is enhanced as polymers and monomers concentrations increase while these parameters decrease in case of increasing crosslinker concentration. The oral biocompatibility results of developed nanogel exhibited no toxicity in rabbits. Histopathological changes were observed between empty and loaded group. The nanosized gel offers a specific surface area which increases the stability of loaded drug (oxaliplatin) and bioavailability of the drug (oxaliplatin) as compared to the conventional drug delivery systems.

Phytochemical Profiling, In Vitro Biological Activities, and In-Silico Studies of Ficus vasta Forssk.: An Unexplored Plant.

Ficus vasta Forssk. (Moraceae family) is an important medicinal plant that has not been previously investigated for its phytochemical and biological potential. Phytochemical screening, total bioactive content, and GCMS analysis were used to determine its phytoconstituents profile. Antioxidant, antibacterial, antifungal, anti-viral, cytotoxicity, thrombolytic, and enzyme inhibition activities were examined for biological evaluation. The plant extract exhibited the maximum total phenolic (89.47 ± 3.21 mg GAE/g) and total flavonoid contents (129.2 ± 4.14 mg QE/g), which may be related to the higher antioxidant potential of the extract. The extract showed strong α-amylase (IC50 5 ± 0.21 µg/mL) and α-glucosidase inhibition activity (IC50 5 ± 0.32 µg/mL). Significant results were observed in the case of antibacterial, antifungal, and anti-viral activities. The F. vasta extract inhibited the growth of HepG2 cells in a dose-dependent manner. The GCMS analysis of the extract provided the preliminary identification of 28 phytocompounds. In addition, the compounds identified by GCMS were subjected to in silico molecular docking analysis in order to identify any interactions between the compounds and enzymes (α-amylase and α-glucosidase). After that, the best-docked compounds were subjected to ADMET studies which provide information on pharmacokinetics, drug-likeness, physicochemical properties, and toxicity. The present study highlighted that the ethanol extract of F. vasta has antidiabetic, antimicrobial, anti-viral, and anti-cancer potentials that can be further explored for novel drug development.

Fourier transform infrared spectrometer analysis and antimicrobial screening of ethanolic extract of Operculina terpathum from cholistan desert.

Aim of present study was to assess pharmacological (antioxidant, antibacterial & antifungal) potential of Operculina terpathum seeds. Ethanolic extract was prepared and its phytochemical evaluation show the different chemical compounds such as carbohydrates, phenols, tannin, flavonoids, cardiac glycosides, steroids, alkaloids and proteins. FTIR spectra showed the presence of organic acids, hydroxyl and phenolic compounds, amino groups, aliphatic compounds, functional groups such as amide, ketone, aldehyde, aromatics and halogen compounds. Antioxidant activity of the Operculina terpathum alcoholic extract was performed by DPPH method and it showed 97.13%whereas IC50±SEM (µg/ml) was 1.425±0.16. Antibacterial activity was performed against different bacterial strains and results were comparable with that of standard. Maximum antibacterial activity was exhibited by Bacillus subtillis (28.33±2 mm) and Bacillus pumilus (25.33±2 mm) respectively. Antifungal activity was also performed and it showed maximum activity against Aspergillus flavous and Candida albicans6±1, 5±1mm respectively. These results showed that Operculina terpathum has good antibacterial and antifungal activity against different microbes and it could be used as an alternative to antibiotics, as the antibiotics resistance is very common now a days.

Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer.

Thyroid cancer in humans has a fast-growing prevalence, with the most common lethal endocrine malignancy for unknown reasons. The current study was aimed to perform qualitative and quantitative investigation and characterization of the gut bacterial composition of euthyroid thyroid cancer patients. The fecal samples were collected from sixteen euthyroid thyroid cancer patients and ten from healthy subjects. The PCR-DGGE was conducted by targetting the V3 region of 16S rRNA gene, as well as real-time PCR for Bacteroides vulgatus, E.coli Bifidobacterium, Clostridium leptum and Lactobacillus were carried. High-throughput sequencing of V3+V4 region of 16S rRNA gene was performed on Hiseq 2500 platform on 20 (10 healthy & 10 diseased subjects) randomly selected fecal samples. The richness indices and comparative diversity analysis showed significant gut microbial modification in euthyroid thyroid cancer than control. At phylum level, there was significant enrichment of Firmicutes, Verrucomicrobia, while a significant decrease in Bacteroidetes was detected in the experimental group. At family statistics, significant high levels of Ruminococcaceae and Verrucomicrobiaceae, while the significant lower abundance of Bacteroidaceae, Prevotellaceae, Porphyromonadaceae, and Alcaligenaceae was after observed. It also found that the significantly raised level of Escherichia-Shigella, Akkermansia [Eubacterium]_coprostanoligenes, Dorea, Subdoligranulum, and Ruminococcus_2 genera, while significantly lowered genera of the patient group were Prevotella_9, Bacteroides and Klebsiella. The species-level gut microbial composition showed a significantly raised level of Escherichia coli in euthyroid thyroid cancer. Thus, this study reveals that euthyroid thyroid cancer patients have significant gut microbial dysbiosis. Moreover, Statistics (P<0.05) of each gut microbial taxa were significantly changed in euthyroid thyroid cancer patients. Therefore, the current study may propose new approaches to understanding thyroid cancer patients' disease pathways, mechanisms, and treatment.

Formulation and evaluation of antiviral drug sofosbuvir fast dissolving tablets using natural super disintegrants.

The main objective of this study to formulate of fast dissolving tablets of sofosbuvir, an antiviral drug used for hepatitis C virus. The direct compression method was employed for the formulation of sofosbuvir FDT and optimized for weight variation test, thickness, hardness, friability, wetting time, water absorption ratio, in-vitro disintegration test, and in-vitro dissolution studies, assay identification by using HPLC and stability studies. Master formulation of F4, Sofosbuvir showed promising results compared to others formulations and selected as the most suitable and best formulation among them. It also has better efficacy, disintegration and dissolution time. F4 was fabricated with both super disintegrants like croscarmellose sodium and sodium starch glycolate that lead to its required features. This formulation would be a good alternate for the management of viral diseases with better dissolution profile, stability and improved bioavailability for the patients.

Physicochemical, antidiarrheal and antidiabetic potential of super food (Moringa oleifera Lam.).

There is a long history of natural products for the treatment of infections and diseases. The objective of present study was to investigate the organoleptic, microscopic, physico-chemical, phytochemical, antidiarrheal and antidiabetic potential of leaf, flowering bud and stem bark of Moringa oleifera L. Macroscopic, microscopic, physico-chemical parameters and phytochemical screening were carried out. Diarrhea was induced with castor oil (10ml/kg), verapamil (3, 10 and 30mg/kg) were used as standard antidiarrheal drug and extract of Moringa oleifera at (100, 300 and 1000mg/kg) was used for treatment. Alpha glucosidase inhibitory assay was carried out by using acarbose (0.5mM) and extracts (5.0 mg/Ml). Diabetes was induced by alloxan (150mg/kg), while glibenclamide (10mg/kg) was used as standard drug, and extracts (at the doses of 500mg/kg) were used to determine the antidiabetic activity. Results showed the presence of primary and secondary metabolites, treatment at the dose of 1.0g/kg of leaf, flowering bud and stem bark showed 94 ±2.527, 85.42±5.460 and 84.58±6.138% protection respectively whereas verapamil (10mg/kg) showed 94.84±3.27% protection. Alpha glucosidase inhibition of stem bark (0.5mg/ml) was 95.43±1.47 and flowering bud 94.78±1.25 whereas acarbose (5mM) inhibition was 92.23±0.14%. Stem bark and flowering bud extract (500mg/kg) decreases the blood glucose level from 388.5±35.83 to 226.3±47.10 and 322.5±48.35 to 173.8±29.5 respectively whereas glibenclamide (10 mg/kg) decreases the blood glucose level from 320.7±22.9 to 146.3±17.7 and increases the body weight of the experimental animal. It was concluded from the results that stem bark has strong antidiabetic potential while leaves of the plant have promising antidiarrheal effect.

Chitosan Elicitation Impacts Flavonolignan Biosynthesis in Silybum marianum (L.) Gaertn Cell Suspension and Enhances Antioxidant and Anti-Inflammatory Activities of Cell Extracts.

Silybum marianum (L.) Gaertn is a rich source of antioxidants and anti-inflammatory flavonolignans with great potential for use in pharmaceutical and cosmetic products. Its biotechnological production using in vitro culture system has been proposed. Chitosan is a well-known elicitor that strongly affects both secondary metabolites and biomass production by plants. The effect of chitosan on S. marianum cell suspension is not known yet. In the present study, suspension cultures of S. marianum were exploited for their in vitro potential to produce bioactive flavonolignans in the presence of chitosan. Established cell suspension cultures were maintained on the same hormonal media supplemented with 0.5 mg/L BAP (6-benzylaminopurine) and 1.0 mg/L NAA (α-naphthalene acetic acid) under photoperiod 16/8 h (light/dark) and exposed to various treatments of chitosan (ranging from 0.5 to 50.0 mg/L). The highest biomass production was observed for cell suspension treated with 5.0 mg/L chitosan, resulting in 123.3 ± 1.7 g/L fresh weight (FW) and 17.7 ± 0.5 g/L dry weight (DW) productions. All chitosan treatments resulted in an overall increase in the accumulation of total flavonoids (5.0 ± 0.1 mg/g DW for 5.0 mg/L chitosan), total phenolic compounds (11.0 ± 0.2 mg/g DW for 0.5 mg/L chitosan) and silymarin (9.9 ± 0.5 mg/g DW for 0.5 mg/L chitosan). In particular, higher accumulation levels of silybin B (6.3 ± 0.2 mg/g DW), silybin A (1.2 ± 0.1 mg/g DW) and silydianin (1.0 ± 0.0 mg/g DW) were recorded for 0.5 mg/L chitosan. The corresponding extracts displayed enhanced antioxidant and anti-inflammatory capacities: in particular, high ABTS antioxidant activity (741.5 ± 4.4 µM Trolox C equivalent antioxidant capacity) was recorded in extracts obtained in presence of 0.5 mg/L of chitosan, whereas highest inhibitions of cyclooxygenase 2 (COX-2, 30.5 ± 1.3 %), secretory phospholipase A2 (sPLA2, 33.9 ± 1.3 %) and 15-lipoxygenase (15-LOX-2, 31.6 ± 1.2 %) enzymes involved in inflammation process were measured in extracts obtained in the presence of 5.0 mg/L of chitosan. Taken together, these results highlight the high potential of the chitosan elicitation in the S. marianum cell suspension for enhanced production of antioxidant and anti-inflammatory silymarin-rich extracts.

Phytochemical, antimicrobial and time-kill kinetics potentials of Euphorbia nivulia Buch.-Ham.: A Cholistan desert medicinal plant.

Euphorbia nivulia a locally occurring plant species possesses antiseptic, analgesic and anti-inflammatory properties and is ethnopharmacologically used in various ailments like skin, ear disorders, boils, and worm infestation. Preliminary phytochemical screening showed presence of flavonoids, polyphenolics, glycosides, alkaloids, tannins and triterpenoids in (70% aqueous-ethanolic) Euphorbia nivulia crude extract (En cr) and its four fractions, i.e., hexane fraction (En hex), butanol fraction (En bt), chloroform fraction (En ch), and aqueous fraction (En aq). In current study, Agar well diffusion and time-kill kinetic assays were performed for antimicrobial activity. 300 mg/ml concentration showed maximum inhibitory zone. Highest zone of inhibition (15.5mm) was demonstrated by En ch fraction against Proteus mirabilis. Staphyllococcus aureus was the most sensitive bacteria against whom all fractions except En aq fraction were active. Maximum MIC (15.3 mg/ml) was shown by En ch fraction against Proteus mirabilis. Similarly, En ch fraction showed (15.1 mg/ml) remarkable MIC against Candida albicans. Significant higher antibacterial and antifungal activity was revealed in high concentration. Time-kill kinetics studies revealed bacteriostatic action. Noteworthy antimicrobial activity may be due to bioactive compounds of extract which may be a potential antibacterial and antifungal agent.

Pediatric oropharyngeal candidiasis: A comprehensive study on risk factors and most prevalent species of Candida.

Oropharyngeal candidiasis is caused by opportunistic fungal pathogen candida. Decreased immune level whether in immunocompromised patients or in extreme age groups facilitate the progression of disease in vulnerable individuals. Current study focusses on evaluation of most prevalent species of Candida in pediatric patients and also assesses risk factors causing oropharyngeal candidiasis. Total of 1152 pediatric patients, previously diagnosed with oropharyngeal candidiasis from rural areas of District Bahawalpur were included in this study. Oral clinical swab samples were collected from these patients. From collected clinical swab samples, isolation, characterization and identification of Candida spp. was carried out to assess most prevalent species. Questionnaire was filled, with prior patients consent, for assessment of risk factors associated with oropharyngeal candidiasis. Candida albicans was the most prevalent species with 68.6% prevalence. While C. lusitaniae (a nonalbicans) was the least prevalent with 0.4% prevalence. Among other non-albicans, C. glabrata counted 12.9%, C. tropicalis 5.6%, C. krusei 8.5%, C. parapsilosis 3.1% and C. dublineiensis 1.1%. Associated risk factors included hygienic status of mother, patient's cleanliness and economic condition of the parents. Being disease of infancy, oropharyngeal candidiasis, is the oral infection with many episodes of relapse in pediatric patients and if not addressed properly may lead to severe invasive and noninvasive infections. There is dire need of integrated efforts to reduce the burden of infections in pediatrics specially and common population in general, by adopting various steps including more awareness programs, increasing economic status of the people, patient counselling and many other steps in rural areas.

Synthesis, spectroscopic, X-ray crystal structure, biological and DNA interaction studies of organotin(IV) complexes of 2-(4-ethoxybenzylidene) butanoic acid.

Six organotin(IV) carboxylates of the type R2SnL2 [R=CH3 (1), n-C4H9 (2), n-C8H17 (3)] and R3SnL [R=CH3 (4), n-C4H9 (5), C6H5 (6), where L=2-(4-ethoxybenzylidene) butanoic acid, have been synthesized and characterized by elemental analysis, FT-IR and NMR ((1)H, (13)C). The complex (1) was also analyzed by single crystal X-ray analysis. The complexes were screened for antimicrobial, cytotoxic and anti-tumor activities. The results showed significant activity in each area of the activity with few exceptions. DNA interactions studies of ligand HL and representative complex 2 were investigated by UV-Visible absorption spectroscopy and viscosity measurements. The results showed that both ligand HL and complex 2 interact with SS-DNA via intercalation as well as minor groove binding.

Beneficial effects of lactic acid bacteria on human beings.

Lactic acid bacteria are a diverse group of bacteria that produce lactic acid as their major fermented product. Most of them are normal flora of human being and animals and produce myriad beneficial effects for human beings include, alleviation of lactose intolerance, diarrhea, peptic ulcer, stimulation of immune system, antiallergic effects, antifungal actions, preservation of food, and prevention of colon cancer. This review highlights the potential species of Lactic acid bacteria responsible for producing these effects. It has been concluded that lactic acid bacteria are highly beneficial microorganisms for human beings and are present abundantly in dairy products so their use should be promoted for good human health.