Quality of life and wellbeing among breast cancer patients in Lahore, Pakistan.

Background: Breast cancer has a high incidence rate, emphasizing the necessity of enhanced information on health-related quality of life (HrQOL) in this population of patients. The aim of this study was to identify the factors influencing the QOL experienced by patients in Pakistan. Methods: A cross-sectional study was conducted on women with breast cancer, and four instruments were used on a random sample of 130 Pakistani women: FACIT-B Version 4 questionnaire,WHO causality assessment scale, Naranjo's algorithm, and a demographic/clinical characteristics section. Data analysis included descriptive analysis, independent sample t-test, and analysis of variance (ANOVA) test. Results: The patients' mean age was 49.10 (standard deviation (SD) 10.89); 98.5% were married. The mean score was 18.34 for physical wellbeing (SD 5.92; interquartile range (IQR) 11), 16.33 for social/family wellbeing (SD 6.3; IQR 11.25), 13.6 for emotional wellbeing (SD 3.55; IQR 6), 17.13 for functional wellbeing (SD 3.73; IQR 6), and 24.86 for breast cancer subscale (SD 3.64; IQR 4). The study found that the age, entitlement, recurrence, marital status, salary, number of doses, duration of cancer treatment, and chemotherapy sessions were significantly related to QOL terms in the assessment of the FACIT-B scale. The WHO causality evaluation scale determined that 78.1% of the responses were "probable" and 20.1% were "possible". According to Naranjo's algorithm assessment scale, 80% of adverse drug reactions (ADRs) were "probable", whereas 18.4% were declared "possible". Chemotherapy-induced anemia was the most often reported ADR in 64.6% of patients, followed by chemotherapy-induced nausea and vomiting (61.5%). Conclusion: Healthcare practitioners must acknowledge and take into account the significance of QOL in addition to therapy for breast cancer patients in order to enhance their health. The findings of this study will aid in filling gaps in current unknown knowledge and identifying sites where patients require additional assistance. Because cancer and chemotherapy clearly have a negative impact on individuals' QOL, oncologists must concentrate on strategies that help cancer patients during their sickness and treatment while also enhancing self-care and QOL. Those with cancer will benefit from emotional wellbeing and adaptation to their disease.

Rapid and ultrasensitive solution-based SERS detection of drug additives in aquaculture by using polystyrene sulfonate modified gold nanobipyramids.

In recent years, surface-enhanced Raman spectroscopy (SERS) has been widely used in various fields for the rapid detection of trace-level molecular targets. In this study, we have developed a simple and effective solution-based SERS protocol to improve the activity for the detection of cationic dye molecules in aquaculture. The polystyrene sulfonate functionalized gold nanobipyramids (PSS-Au BPs) were synthesized from the cetyltrimethylammonium bromide (CTAB) reaction system followed by the ligand exchange process. The halide ions-induced aggregation of PSS-Au BPs was carried out by using four type of different salts such as NaCl, NaBr, MgCl2 and MgSO4 to investigate their influence on the SERS activity. The results demonstrate that the ionic strength of the solution has an important impact on the colloidal stability and SERS activity. The PSS-Au BPs show an improved SERS sensitivity at lower concentrations of the aggregating agents in solution-based SERS by detecting the crystal violet (CV) molecules with a limit of detection (LOD) to 3.28 × 10-11 M. Furthermore, to demonstrate the generality of our proposed strategy, trace amounts of three more dyes such as malachite green (MG), methylene blue (MB), and rhodamine 6G (R-6G), as well as other molecules such as thiram and bisphenol-S were also detected. This protocol not only provides a method for rapid on-site detection of trace-level molecules but can also be applied to other SERS-based analysis.

Ameliorative effect of two structurally divergent hydrazide derivatives against DSS-induced colitis by targeting Nrf2 and NF-κB signaling in mice.

The environmental factors and genetic vulnerability trigger the inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease. Furthermore, the oxidative stress and inflammatory cytokines have been implicated in the aggravation of the IBDs. The aim of the present study was to investigate the effect of N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (NCHDH and NTHDH) compounds against the DSS-induced colitis in mice. The colitis was induced by 5% dextran sulfate sodium (DSS) dissolved in normal saline for 5 days. The effect of the NCHDH and NTHDH on the behavioral, biochemical, histological, and immunohistological parameters was assessed. The NCHDH and NTHDH treatment improved the behavioral parameters such as food intake, disease activity index, and diarrhea score significantly compared to DSS control. The NCHDH and NTHDH treatments significantly increased the antioxidant enzymes, whereas oxidative stress markers were markedly reduced. Similarly, the NCHDH and NTHDH treatments significantly suppressed the activity of nitric oxide (NO), myeloperoxidase (MPO), and eosinophil peroxidase (EPO). The histological studies showed a significant reduction in inflammation, immune cell infiltration, and fibrosis in the NCHDH- and NTHDH-treated groups. The immunohistochemical results demonstrated that NCHDH and NTHDH treatments markedly increase the expression level of Nrf2, HO-1 (hemeoxygenase-1), TRX (thioredoxin reductase), and IκB compared to the DSS-induced group. In the same way, the NCHDH and NTHDH significantly reduced the NF-κB and COX-2 (cyclooxygenase-2) expression levels. The NCHDH and NTHDH treatment significantly improved the symptoms associated with colitis via inducing antioxidants and attenuating oxidative stress markers.

A qualitative insight into the perceptions and COVID-19 vaccine hesitancy among Pakistani pharmacists.

A qualitative exploration of pharmacists' perceptions regarding COVID-19 conspiracies and their willingness to get vaccinated. A semi-structured questionnaire guide was developed using ground theory to conduct in-depth interviews. A total of 36 participants gave consent for an audio-recorded interview. Results have shown that most of the respondents believed that SARS-CoV-2 is a natural virus, not man-made, that causes a disease just like other viruses and it is absurd to believe that the vaccine is being used by foreign powers for the implantation of microchips just to control humans. A general opinion thatwhich reflected from the in-depth interview is that the pharmaceutical companies may be hiding some important information on COVID-19 to promote the sale of their product. Some doubts on the reliability and trustworthiness on the COVID-19 vaccine safety and efficacy data were noticed among the respondents. Factors leading to COVID-19 vaccine hesitancy were adverse reaction, cost of COVID-19 vaccine, and limited data on safety and efficacy profile of COVID-19 vaccine. COVID-19 vaccine hesitancy among health professionals is a major hindrance to our current fight against COVID-19 pandemic. Findings of this study are alarming, and the stakeholders must consider this ongoing vaccination campaign as an opportunity to formulate a mechanism to ensure high vaccination rate among general public and healthcare providers in Pakistan.KEY POINTSWhat was already known?According to World Health Organization (WHO), vaccine hesitancy is one of the ten major threats to global healthcare system and it is a major barrier to achieve herd immunity around the globe.Pakistan has begun vaccinating its people in a systematic phase-wise manner under which the healthcare workers and elderly people are prioritized for vaccination.Previous experience tells us that vaccine hesitancy is a major problem in Pakistan and it is better to understand perceptions of pharmacists about COVID-19 vaccine who are the primary source of information for most of general population.What this study adds:This study is first of its kind to explore vaccine hesitancy among Pakistani pharmacists and the results of this study show that majority of the participants were willing to get COVID-19 vaccine and few of them have even got themselves vaccinated at the start of vaccination campaign.Many among the willing participants considered cost of vaccine, adverse reactions, limited data, safety, and efficacy as major hindrance to their decision to get vaccine.Few participants were found highly vaccine-hesitant because of their staunch belief in the prevalent myths and rumors about COVID-19 vaccine.

Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (ß-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.

Switchable Binding Energy of Ionic Compounds and Application in Customizable Ligand Exchange for Colloid Nanocrystals.

The ability to engineer the surface ligands or adsorbed molecules on colloid nanocrystals (NCs) is important for various applications, as the physical and chemical properties are strongly affected by the surface chemistry. Here, we develop a facile and generalized ionic compound-mediated ligand-exchange strategy based on density functional theory calculations, in which the ionic compounds possess switchable bonding energy when they transfer between the ionized state and the non-ionized state, hence catalyzing the ligand-exchange process. By using an organic acid as the intermediate ligand, ligands such as oleylamine, butylamine, polyvinylpyrrolidone, and poly(vinyl alcohol) can be freely exchanged on the surface of Au NCs. Benefiting from this unique ligand-exchange strategy, the ligands with strong bonding energy can be replaced by weak ones, which is hard to realize in traditional ligand-exchange processes. The ionic compound-mediated ligand exchange is further utilized to improve the catalytic properties of Au NCs, facilitate the loading of nanoparticles on substrates, and tailor the growth of colloid NCs. These results indicate that the mechanism of switchable bonding energy can be significantly expanded to manipulate the surface property and functionalization of NCs that have applications in a wide range of chemical and biomedical fields.

Solution-Based SERS Detection of Weak Surficial Affinity Molecules Using Cysteamine-Modified Au Bipyramids.

To achieve ultrasensitive detection of trace targets through solution-based surface-enhanced Raman spectroscopy (SERS), direct adsorption of the target molecules on a SERS-active surface is vital. In this work, cetyltrimethylammonium bromide (CTAB)-capped gold nano-bipyramids (Au BPs) with different aspect ratios (ARs) are prepared and the surface is successfully modified by a simple ligand exchange method. Cysteamine-capped gold nano-bipyramids (cyst-Au BPs) are obtained by means of replacement of CTAB by cysteamine using Au-S covalent bonding and applied in the solution-based SERS detection of different pigment molecules, which always have weak affinity to the gold surface. The hydrogen bonding between the pigment molecule and cysteamine causes the aggregation of Au BPs to generate local electromagnetic field enhancement. The influence of the AR and concentration of Au BPs on SERS properties is investigated. The SERS detection of weak-affinity molecules to an extremely low limit shows that the cyst-Au BPs are highly sensitive compared to CTAB-capped Au BPs. The limit of detection (LOD) of allura red as low as 0.1 ppb and that of sunset yellow as low as 1 ppb show that the proposed strategy has many advantages due to its simplicity and fast and rapid detection for the sensitivity analysis of weak-affinity molecules.

A novel gabapentin analogue assuages neuropathic pain response in chronic sciatic nerve constriction model in rats.

Gabapentin (GBP) is an established drug that has been used in the management of symptoms of neuropathy but it is associated with unwanted side effects such as sedation and motor incoordination. The goal of the study was to find out a drug with greater efficacy and safety for the treatment of neuropathic pain. Our previously synthesized GABA analogue (Gabapentsal, GPS) was tested (25-100 mg/kg, i.p) in chronic constriction injury (CCI) induced nociceptive model of static allodynia, dynamic allodynia, thermal hyperalgesia, mechanical hyperalgesia and cold allodynia in rats (Sprague Dawley). Open field and rotarod tests were performed to assess the impact of GPS on the motor performance of the animals. GBP (100 mg/kg, i.p) was used as a standard for comparison. GPS dose dependently reduced static (P <0.001) and dynamic allodynia (P <0.001), thermal hyperalgesia (P <0.001), mechanical hyperalgesia (P < 0.001) and cold allodynia (P < 0.001). In comparison to GBP, GPS failed to alter any significantly the motor performance of rats in both the open field and rotarod assays. These results suggest that GPS is effective in alleviating nociception in CCI neuropathic pain model but free from the side effect of motor discoordination seen in the treatment with GBP. In conclusion, GPS may prove to be a prospectively more effective and safer option in the management of neuropathic syndromes.

Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative.

Alzheimer's disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC50 values of the 3NCP against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were 16.17 and 20.51 µg/mL, respectively. This decline in AChE and BChE was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.

Antimicrobial, Cytotoxic, and Antioxidant Potential of a Novel Flavone "6,7,4'-Trimethyl Flavone" Isolated from Wulfenia amherstiana.

Wulfenia amherstiana belongs to the Scrophulariaceae family and various plants of this family are known for their biological activities. The present study was focused on the isolation of bioactive compounds including a novel flavone 6,7,4'-trimethyl flavone (TMF) along with three known flavonoids such as quercetin, rutin, and a steroid ß-sitosterol which were isolated from the ethanolic extract of W. amherstiana (Himalayan Wulfenia) through column chromatography and purified by using HPLC. Their structures were identified and elucidated through electron ionization mass spectroscopy (EIMS), 1DNMR (1H-NMR and 13C-NMR), and 2DNMR (COSY, HMQC, and HMBC) spectroscopy. The antimicrobial activities of this novel compound were evaluated through agar well diffusion method, while antioxidant and cytotoxic activities were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging assay and brine shrimp lethality assay, respectively. The NMR data revealed that TMF is a novel compound. TMF showed potential antibacterial and antifungal activities against Staphylococcus aureus (MIC = 128 µg/ml) and Candida albicans (MIC = 128 µg/ml). The cytotoxic potential of TMF was determined from brine shrimp lethality assay with LD50 of 127.01 µg/ml. The free-radical scavenging potential of TMF at various concentrations implicated its strong antioxidant activity in vitro. The results revealed that TMF demonstrated substantial antimicrobial activity against S. aureus and C. albicans, strong antioxidant activity, and moderately cytotoxic activity.

Novel nonsense IL-12Rß1 mutation associated with recurrent tuberculosis.

The interleukin (IL)-12/interferon(IFN)γ axis plays an important role in the control of mycobacterial diseases as demonstrated by the increased susceptibility to mycobacterial species in patients with an inborn error of the IL-12-dependent IFNγ immunity. Here, we report a novel mutation in the IL-12Rß1 gene in a female Pakistani patient who was born in a consanguineous marriage and developed severe bacille Calmette-Guérin (BCG) infection and recurrent tuberculosis. After reviewing the patient's clinical records, she was investigated for IL-12/IFNγ defects using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and DNA genetic Sanger sequencing. Quantification of secretory cytokines from the patient's peripheral blood mononuclear cells (PBMCs) revealed significantly reduced IFNγ production. Flow cytometric analysis revealed no surface expression of IL-12Rß1 on PHA-activated T lymphocytes. In addition, IL-12-induced impaired STAT4 phosphorylation in the patient's lymphocytes when compared with those from five healthy controls. The genetic analysis of IL-12Rß1 gene identified a novel nonsense mutation c.199G>T/p.E67* within exon 3, which encodes part of the cytokine-binding region (CBR). In silico analysis indicates that this novel nonsense mutation generates a truncated protein with an apparent inactivating effect. Our data expand the genetic spectrum of IL-12Rß1 deficiency. Moreover, our findings highlight the need for developing newborn screening for patients with primary immunodeficiency associated with mycobacterial infections in areas where BCG vaccination is mandatory in order to improve the treatment of patients, and consequently their quality of life.

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity.

BACKGROUND: Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. METHODS: Semi-crystalline nanoparticles (NPs) of 90-110 nm diameter for APSP and 65-75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. RESULTS: The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. CONCLUSION: Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

Fabrication, characterization and in vitro evaluation of silibinin nanoparticles: an attempt to enhance its oral bioavailability.

BACKGROUND: Silibinin has gained in importance in the past few decades as a hepatoprotector and is used widely as oral therapy for toxic liver damage, liver cirrhosis, and chronic inflammatory liver diseases, as well as for the treatment of different types of cancers. Unfortunately, it has low aqueous solubility and inadequate dissolution, which results in low oral bioavailability. MATERIALS AND METHODS: In this study, nanoparticles (NPs) of silibinin, which is a hydrophobic drug, were manufactured using two cost-effective methods. Antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN) were used. The prepared NPs were characterized using different analytical techniques such as scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffractometry (XRD) and were sifted for their bioavailability through in vitro dissolution and solubility studies. Moreover, the prepared NPs were evaluated for antimicrobial activity against a battery of bacteria and yeast. RESULTS: DSC and XRD studies indicated that the prepared NPs were amorphous in nature, with more solubility and dissolution compared to the crystalline form of this drug. NPs prepared through the EPN method had better results than those prepared using the APSP method. Antimicrobial activities of the NPs were improved compared to the unprocessed drugs, while having comparable activities to standard antimicrobial drugs. CONCLUSION: Results indicate that the NPs have significantly increased solubility, dissolution rate, and antimicrobial activities due to the conversion of crystalline structure into amorphous form.

A novel missense mutation in the NADPH binding domain of CYBB abolishes the NADPH oxidase activity in a male patient with increased susceptibility to infections.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the five structural genes (CYBB, CYBA, NCF1, NCF2, and NCF4) that typically results in a decrease in function or inability to generate a respiratory burst, leading to defective killing of pathogens, including fungi and intracellular bacteria. Mutations in CYBB, encoding the gp91phox (also known as NOX2) result in X-linked CGD account for approximately 65% of CGD cases. Here, we aimed the characterization of a novel missense mutation c.1226C > A/p.A409E in the CYBB gene in a patient with X-linked CGD. Relevant clinical data of a male patient whose family was positive for XCGD was reviewed. Oxidative burst and NADPH protein expression was evaluated by flow cytometry, while Genetic analysis was performed by Sanger sequencing. Monocyte-derived macrophages (MDMs) were evaluated for their capacity for phagocytosis and growth suppression of the intracellular Mycobacterium tuberculosis (M. tuberculosis). We thus report the absence of an oxidative burst in the phagocytes of the patient. Flow cytometry evaluation revealed a normal expression of NADPH oxidase components in neutrophils and genetic analysis proved the existence of a novel missense c.1226C > A mutation in the CYBB gene resulting in p.A409E. Further, we have showed that the patient's MDMs were unhindered in their ability to take up mycobacteria normally. Instead, the MDMs failed to control the intracellular proliferation of M. tuberculosis, a phenotype that improved in the presence of recombinant human interferon-gamma (rhIFN-γ). This work expands the genetic spectrum of X-linked CGD and demonstrates improvement in macrophage function in X91+CGD patient by rhIFN-γ.

Antibiotic additive and synergistic action of rutin, morin and quercetin against methicillin resistant Staphylococcus aureus.

BACKGROUND: To determine the effect of flavonoids in conjunction with antibiotics in methicillin resistant Staphylococcus aureus (MRSA) a study was designed. The flavonoids included Rutin, Morin, Qurecetin while antibiotics included ampicillin, amoxicillin, cefixime, ceftriaxone, vancomycin, methicillin, cephradine, erythromycin, imipenem, sulphamethoxazole/trimethoprim, ciprofloxacin and levolfloxacin. Test antibiotics were mostly found resistant with only Imipenem and Erythromycin found to be sensitive against 100 MRSA clinical isolates and S. aureus (ATCC 43300). The flavonoids were tested alone and also in different combinations with selected antibiotics. METHODS: Antibiotics and flavonoids sensitivity assays were carried using disk diffusion method. The combinations found to be effective were sifted through MIC assays by broth macro dilution method. Exact MICs were determined using an incremental increase approach. Fractional inhibitory concentration indices (FICI) were determined to evaluate relationship between antibiotics and flavonoids is synergistic or additive. Potassium release was measured to determine the effect of antibiotic-flavonoids combinations on the cytoplasmic membrane of test bacteria. RESULTS: Antibiotic and flavonoids screening assays indicated activity of flavanoids against test bacteria. The inhibitory zones increased when test flavonoids were combined with antibiotics facing resistance. MICs of test antibiotics and flavonoids reduced when they were combined. Quercetin was the most effective flavonoid (MIC 260 µg/ml) while morin + rutin + quercetin combination proved most efficient with MIC of 280 + 280 + 140 µg/ml. Quercetin + morin + rutin with amoxicillin, ampicillin, cephradine, ceftriaxone, imipenem, and methicillin showed synergism, while additive relationship was indicated between morin + rutin and amoxicillin, cephradine, ceftriaxone, imipenem, and methicillin. Quercetin alone had an additive effect with ampicillin, cephradine, ceftriaxone, imipenem, and methicillin. Potassium leakage was highest for morin + rutin + quercetin that improved further in combination with imipenem. Morin and rutin alone had no activity but in combination showed activity against test bacteria. CONCLUSIONS: The flavonoids when used in combination with antibiotics were found to increase each other activity against test bacteria. The relationship between the flavonoids and antibiotics in most of the cases was additive. However in a few cases synergism was also observed. Flavonoids alone or in combinations also damaged bacterial cell membrane.