Phytomedicines: Synergistic and antagonistic phytometabolites-drug interactions
Abstract
Phytometabolites-drug interactions, when administered concurrently, may affect the body's ability to metabolize the medication or provoke critical side repercussions. Clinically considerable medicament interactions present a potential danger to the sick person and may lead to alterations in pharmaceutical, pharmacokinetic, or pharmacodynamic features. Nourishment and way of living can occasionally have a considerable effect on medication. This chapter is structured in two parts, based on a study of the production mode as well as the factors favoring the production of phytometabolite-drug interactions, comprising: general aspects regarding the production of phytometabolite-drug interactions, the changes produced by medication, aspire to nutritional status, the effect of phytometabolites and their compounds in drug metabolism, and the interaction of grapefruit juice with certain classes of drugs to avoid accidents caused by active medications in an inappropriate dietary context, and the part that includes the mechanism of producing the interaction between grapefruit juice and diclofenac (DCF) based on the pharmacokinetic parameters determined experimentally.
This book chapter critically compares the efficacy, mechanisms, and implications of nutritional interventions vs. pharmacological interventions in the management of various psychiatric disorders. It explores the growing body of evidence supporting the therapeutic potential of dietary modifications, supplementation, and nutraceuticals in preventing and treating diseases, alongside traditional pharmacological approaches. The chapter evaluates the strengths and limitations of each approach, highlighting their respective roles in promoting health and combating illness. Furthermore, it examines emerging concepts such as personalized nutrition and integrative medicine, which integrate both nutritional and pharmacological interventions to optimize patient outcomes.
Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin’s potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.
Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.
Plant-based phytochemicals are now being used to treat plenty of physiological diseases. Herbal drugs have gained popularity in recent years because of their strength, purity, and cheap cost-effectiveness. Citrus fruits contain significant amounts of flavanones, which falls to the category of polyphenols. Flavanones occupy a major fraction of the total polyphenols present in the plasma when orange juice is taken highly or in moderate states. Narirutin is a disaccharide derivative available in citrus fruits, primarily dihydroxy flavanone. From a pharmacological viewpoint, narirutin is a bioactive phytochemical with therapeutic efficacy. Many experimental researches were published on the use of narirutin. Anticancer activity, neuroprotection, stress relief, hepatoprotection, anti-allergic activity, antidiabetic activity, anti-adipogenic activity, anti-obesity action, and immunomodulation are a couple of the primary pharmacological properties. Narirutin also has antioxidant, and anti-inflammatory activities. The ultimate goal of this review is to provide the current scenario of pharmacological research with narirutin; to make a better understanding for therapeutic potential of narirutin, as well as its biosynthesis strategies and side effects. Extensive literature searches and studies were undertaken to determine the pharmacological properties of narirutin.
A large number of nutrients and bioactive ingredients found in milk play an important role in the nourishment of breast-fed infants and dairy consumers. Some of these ingredients include physiologically relevant compounds such as vitamins, peptides, neuroactive compounds and hormones. Conversely, milk may contain substances—drugs, pesticides, carcinogens, environmental pollutants—which have undesirable effects on health. The transfer of these compounds into milk is unavoidably linked to the function of transport proteins. Expression of transporters belonging to the ATP-binding cassette (ABC-) and Solute Carrier (SLC-) superfamilies varies with the lactation stages of the mammary gland. In particular, Organic Anion Transporting Polypeptides 1A2 (OATP1A2) and 2B1 (OATP2B1), Organic Cation Transporter 1 (OCT1), Novel Organic Cation Transporter 1 (OCTN1), Concentrative Nucleoside Transporters 1, 2 and 3 (CNT1, CNT2 and CNT3), Peptide Transporter 2 (PEPT2), Sodium-dependent Vitamin C Transporter 2 (SVCT2), Multidrug Resistance-associated Protein 5 (ABCC5) and Breast Cancer Resistance Protein (ABCG2) are highly induced during lactation. This review will focus on these transporters overexpressed during lactation and their role in the transfer of products into the milk, including both beneficial and harmful compounds. Furthermore, additional factors, such as regulation, polymorphisms or drug-drug interactions will be described.
Indiscriminate and incessant use of synthetic pesticides is becoming an increasing global concern. No doubt, the application of conventional synthetic pesticides has enhanced the quality and quantity of agricultural products. However, accumulation of pesticides in freshwater resources has negative effects on aquatic ecosystem and human health. The persistent and toxic nature of pesticides has led to direct or indirect exposure on the biota in aquatic ecosystems resulting in acute (mortality of organisms) and chronic effects (decreased production and change in community structure), thus posing serious consequences for the ecosystem. Biopesticides provides a cost-effective and innovative approach employing bioremediation techniques for the removal of pesticides in water because of its advantage linked with environmental safety, biodegradability, effectiveness, and target-specificity. Furthermore, biopesticides provide an efficient method for detoxification of pesticides and appropriateness in the integrated pest management (IPM) programs.
Phytoremediation is an economic process through exploitation of plants capacity to accumulate heavy
metals in polluted habitats by their harvestable parts. In the present investigation, Portulaca oleracea was
examined to estimate its role in the accumulation of Mn(II), Cu(II), Zn(II), Fe(III) and Pb(II) ions and
recognize its persistence against the industrial effluent toxicity from different farmlands located beside
these regions (S1:S9) in Dakahlia district, Egypt. The most recorded associate plants were; Amaranthus
viridus, Malva parviflora, Chenopodium murale and Echinochloa colonum, which have high potentiality of
heavy metals (HM) accumulation. The phytoremediation efficiency (bioconcentration factor (BCF), bioaccumulation
factor (BF), translocation factor (TF), enrichment coefficient of shoot (ECS) and element
accumulation index (EAI)) of P. oleracea were calculated. Considering the results, S7 showed the highest
BCF value for Cu(II), 7.40; Fe(III), 2.06; and Zn(II), 4.33, while Mn(II), 2.06 at S1 and Pb(II), 3.89 at S3. BF
and TF values were less than unity 1.0 for most of the sites. However, ECS values showed small variations
among the investigated HM at the nine sites. EAI values were higher in shoots out of all the sites except
S2 > EAI of roots of the same sites. Also, there was positive correlation between the soil HM concentrations
in most sites. Moreover, total protein was estimated quantitatively and qualitatively. The protein
profile showed 16 bands of molecular weight ranged from 30.9 to 240.6 KDa. Finally, P. oleracea can be
used for decontamination of soils with heavy metals due to the high ecological amplitude and phytoremediation
characteristics.
This study investigated the treatment performance and nitrogen removal mechanism of highly alkaline ammonia-stripped digestate effluent in horizontal subsurface flow constructed wetlands (CWs). A promising nitrogen removal performance (up to 91%) was observed in CWs coupled with intensified configurations, i.e., aeration and effluent recirculation. The results clearly supported that the higher aeration ratio and presence of effluent recirculation are important to improve the alkalinity and pollutant removal in CWs. The influent pH (>10) was significantly decreased to 8.2–8.8 under the volumetric hydraulic loading rates of 0.105 and 0.21 d−1 in the CWs. Simultaneously, up to 91% of NH4+-N removal was achieved under the operation of a higher aeration ratio and effluent recirculation. Biological nitrogen transformations accounted for 94% of the consumption of alkalinity in the CWs. The significant enrichment of δ15N-NH4+ in the effluent (47–58‰) strongly supports the occurrence of microbial transformations for NH4+-N removal. However, relatively lower enrichment factors of δ15N-NH4+ (−1.8‰ to −11.6‰) compared to the values reported in previous studies reflected the inhibition effect of the high pH alkaline environment on nitrifiers in these CWs.
Technologies are available which will allow the conversion of lignocellulose into fuel ethanol using genetically engineered bacteria. Assembling these into a cost-effective process remains a challenge. Our work has focused primarily on the genetic engineering of enteric bacteria using a portable ethanol production pathway. Genes encoding Zymomonas mobilis pyruvate decarboxylase and alcohol dehydrogenase have been integrated into the chromosome of Escherichia coli B to produce strain KO11 for the fermentation of hemicellulose-derived syrups. This organism can efficiently ferment all hexose and pentose sugars present in the polymers of hemicellulose. Klebsiella oxytoca M5A1 has been genetically engineered in a similar manner to produce strain P2 for ethanol production from cellulose. This organism has the native ability to ferment cellobiose and cellotriose, eliminating the need for one class of cellulase enzymes. The optimal pH for cellulose fermentation with this organism (pH 5.0–5.5) is near that of fungal cellulases. The general approach for the genetic engineering of new biocatalysts has been most successful with enteric bacteria thus far. However, this approach may also prove useful with Gram-positive bacteria which have other important traits for lignocellulose conversion. Many opportunities remain for further improvements in the biomass to ethanol processes. These include the development of enzyme-based systems which eliminate the need for dilute acid hydrolysis or other pretreatments, improvements in existing pretreatments for enzymatic hydrolysis, process improvements to increase the effective use of cellulase and hemicellulase enzymes, improvements in rates of ethanol production, decreased nutrient costs, increases in ethanol concentrations achieved in biomass beers, increased resistance of the biocatalysts to lignocellulosic-derived toxins, etc. To be useful, each of these improvements must result in a decrease in the cost for ethanol production. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 58:204–214, 1998.
In India, traditional herbal medicines have been an essential part of therapy for the last centuries. However, a large portion of the general populace is using these therapies in combination with allopathy lacking a proper understanding of possible interactions (synergistic or antagonistic) between the herbal product and the allopathic drug. This is based on the assumption that herbal drugs are relatively safe, i.e. without side effects. We have established a comprehensive understanding of the possible herb-drug interactions and identified interaction patterns between the most common herbs and drugs currently in use in the Indian market. For this purpose, we listed common interactors (herbs and allopathic drugs) using available scientific literature. Drugs were then categorized into therapeutic classes and aligned to produce a recognizable pattern present only if interactions were observed between a drug class and herb in the scientific literature. Interestingly, the top three categories (with highest interactors), antibiotics, oral hypoglycemics, and anticonvulsants, displayed synergistic interactions only. Another major interactor category was CYP450 enzymes, a natural component of our metabolism. Both activation and inhibition of CYP450 enzymes were observed. As many allopathic drugs are known CYP substrates, inhibitors or inducers, ingestion of an interacting herb could result in interaction with the co-administered drug. This information is largely unavailable for the Indian population and should be studied in greater detail to avoid such interactions. Although this information is not absolute, the systematic literature review proves the existence of herb-drug interactions in the literature and studies where no interaction was detected are equally important.
Nineteen compounds were isolated from the stems of Maackia amurensis by activity-guided screening for new human monoamine oxidase-B (hMAO-B) inhibitors. Among the compounds isolated, flavonoids calycosin (5) and 8-O-methylretusin (6) were found to potently and selectively inhibit hMAO-B (IC50 = 0.24 and 0.23 μM, respectively) but not hMAO-A with high selectivity index (SI) values (SI = 293.8 and 81.3, respectively). In addition, 5 and 6 reversibly and competitively inhibited hMAO-B with Ki values of 0.057 and 0.054 μM, respectively. A pterocarpan (-)-medicarpin (18) was also observed to strongly inhibit hMAO-B (IC50 = 0.30 μM). Most of the compounds weakly inhibited AChE, except isolupalbigenin (13) (IC50 = 20.6 μM), which suggested 13 be considered a potential dual function inhibitor of MAO-B and AChE. Molecular docking simulation revealed that the binding affinities of 5 and 6 for hMAO-B (both -9.3 kcal/mol) were higher than those for hMAO-A (-7.4 and -7.2 kcal/mol, respectively). Compound 5 was found to interact by hydrogen bonding with hMAO-B at Cys172 residue (distance: 3.250 Å); no hydrogen bonding was predicted between 5 and hMAO-A. These findings suggest that compounds 5 and 6 be considered novel potent, selective, and reversible hMAO-B inhibitors and candidates for the treatment of neurological disorders.
In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co‐administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15‐day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co‐administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high‐performance liquid chromatography. The pharmacokinetic parameters were calculated using a two‐compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half‐life (t1/2β), total body clearance (ClT), volume of distribution at steady state (Vdss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h−1 kg−1, 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2β and AUC of moxifloxacin, they significantly reduced the ClT and Vdss. These results suggest that anti‐inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.