Natural Product Mixtures Research Articles

Computational Tools to Expedite the Identification of Potential PXR Modulators in Complex Natural Product Mixtures: A Case Study with Five Closely Related Licorice Species.

The genus Glycyrrhiza, comprising approximately 36 spp., possesses complex structural diversity and is documented to possess a wide spectrum of biological activities. Understanding and finding the mechanisms of efficacy or safety for a plant-based therapy is very challenging, yet it is crucial and necessary to understand the polypharmacology of traditional medicines. Licorice extract was shown to modulate the xenobiotic receptors, which might manifest as a potential route for natural product-induced drug interactions. However, different mechanisms could be involved in this phenomenon. Since the induced herb–drug interaction of licorice supplements via Pregnane X receptor (PXR) is understudied, we ventured out to analyze the potential modulators of PXR in complex mixtures such as whole extracts by applying computational mining tools. A total of 518 structures from five species of Glycyrrhiza: 183 (G. glabra), 180 (G. uralensis), 100 (G. inflata), 33 (G. echinata), and 22 (G. lepidota) were collected and post-processed to yield 387 unique compounds. Visual inspection of top candidates with favorable ligand–PXR interactions and the highest docking scores were identified. The in vitro testing revealed that glabridin (GG-14) is the most potent PXR activator among the tested compounds, followed by licoisoflavone A, licoisoflavanone, and glycycoumarin. A 200 ns molecular dynamics study with glabridin confirmed the stability of the glabridin-PXR complex, highlighting the importance of computational methods for rapid dereplication of potential xenobiotic modulators in a complex mixture instead of undertaking time-consuming classical biological testing of all compounds in a given botanical.

A Combination of Natural Products, BenPros (Green Tea Extract, Soybean Extract and Camellia Japonica Oil), Ameliorates Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men and causes lower urinary tract symptoms due to excessive proliferation of prostate stromal and epithelial cells. The present study investigated the improving effect of BenPros, an edible natural product mixture (green tea extract, soybean extract and camellia japonica oil), against the development of BPH in vitro and in vivo. BenPros treatment showed inhibitory ability on testosterone-induced androgen receptor, prostate-specific antigen (PSA), and 5α-reductase protein expression in LNCap-LN3 cells and anti-inflammatory effects on LPS-induced increases in interleukin-6 and tumor necrosis factor-α in RAW264.7 cells. In a testosterone propionate (TP)-induced BPH rat model, BenPros decreased the up-regulated serum 5α-dihydrotestosterone and PSA levels. Moreover, BenPros also significantly reduced PSA protein expression in prostate tissue. Furthermore, TP-induced increased expression of cyclooxygenase 2 and B-cell lymphoma 2 (Bcl-2) were reduced by BenPros, resulting in an increase in the Bcl-2/BCL2-related X ratio. These regulatory abilities of BenPros on BPH inducing markers also reduced prostate size and epithelial thickness based on histological analysis. These results indicate that BenPros has a protective ability against BPH in vitro and in vivo, and it may be a promising candidate as a functional food in regulating BPH.

Evaluation of Ion Mobility Spectrometry for Improving Constitutional Assignment in Natural Product Mixtures.

The comprehensive chemical characterization of biological samples remains a central challenge in the field of natural products. Conventional workflows using liquid chromatography (LC)-coupled high-resolution tandem mass spectrometry (MS/MS or MS2) allow the detection of relevant small molecules while providing diagnostic fragment ions for their structural assignment. Still, many natural product extracts are of a molecular complexity that challenges the resolving power of modern LC-MS2 pipelines. In this study, we examined the effect of integrating ion mobility spectrometry (IMS) to our LC-MS2 platform for the characterization of natural product mixtures. IMS provides an additional axis of separation in the gas phase as well as experimental collision cross-sectional (CCS) values. We analyzed a mixture of 20 commercial standards at 2 concentration ranges, either solubilized in solvent or spiked into an actinobacterial extract. Data were acquired in positive ion mode using both data-dependent acquisition (DDA) and data-independent acquisition (DIA) MS2 fragmentation approaches and assessed for both chemical coverage and spectral quality. IMS-DIA identified the largest number of standards in the spiked extract at the lower concentration of standards (17), followed by IMS-DDA (10), DDA (8), and DIA (6). In addition, we examined how these data sets performed in the Global Natural Products Social Molecular Networking (GNPS) platform. Overall, integrating IMS increased both metabolite detection and the quality of MS2 spectra, particularly for samples analyzed in DIA mode.

Evaluation of the Antibacterial and Anti-Inflammatory Effects of a Natural Products-Containing Toothpaste.

Fluoride-containing toothpaste is daily used in toothbrush. Some compounds derived from natural herbs that have antibacterial and anti-inflammatory activities has attracted increasing attention as potential supplements for the control of oral diseases. In this paper, a natural product mixture (NPM-8) containing eight herbs extracts was added to toothpaste, and its antibacterial and anti-inflammatory effects were investigated. The results showed that NPM-8-containing toothpaste exhibited superior and faster inhibitory and bactericidal effects against S. mutans, S. sanguinis and P. gingivalis than that of the NPM-8-free toothpaste. NPM-8-containing toothpaste significantly reduced the biomass of single-species or three-species biofilms. The cytotoxicity of the NPM-8-containing toothpaste was similar to that of the conventional fluoride toothpaste and CHX. The NPM-8-containing toothpaste could significantly inhibit IL-1β and IL-6 production in HGE cells and exhibited a better anti-inflammatory effect than that of the NPM-8-free toothpaste. In conclusion, NPM-8-containing fluoride toothpaste is superior to conventional fluoride toothpaste in regard to their antibacterial, antibiofilm, and anti-inflammatory properties. NPM-8-containing toothpaste also has good biocompatibility and is safe for daily use. It indicates that NPM-8 is a promising natural product mixture in oral health.

Brazilian Cerrado biome essential oils to control the arbovirus vectors Aedes aegypti and Culex quinquefasciatus

Insecticides have been used not only to control pests in agricultural production, but also in integrated vector management strategies to reduce populations of mosquitoes, and, consequently, decrease transmission of pathogens they carry. The Aedes aegypti mosquito is a vector of dengue, Zika, chikungunya and yellow fever viruses, whereas the common mosquito Culex quinquefasciatus is a vector of human filariasis and the West Nile virus. Natural insecticides constitute effective ecofriendly alternatives to synthetic control agents. Thus, we investigated the larvicidal, adulticidal and repellent activity of six Brazilian Cerrado plant essential oils extracted by hydrodistillation, together with their major components identified by GC/MS: p-cymene, (R)-(+)-limonene, (S)-(-)-limonene and (-)-β-pinene. The species were selected taking into account the fact they are plants commonly found in this biome, easy to be collected and being still poorly studied in terms of their activity in the Ae. aegypti and Cx. quinquefasciatus. These essential oils demonstrated activity against (i) Ae. aegypti larvae (24 h): Xylopia aromatica (LC50 12.1 µg/mL), Myrcia dictyophylla (LC50 17.6 µg/mL) and Campomanesia adamantium (LC50 18.0 µg/mL); and (ii) Ae. aegypti adults (after 4 h exposure) with the highest knockdown values observed for C. adamantium (93.8%), Blepharocalyx salicifolius (93.4%), M. dictyophylla (92.5%) and X. aromatica (87.2%). These natural product mixtures also demonstrated repellency to (i) Ae. aegypti: Eugenia dysenterica leaves: spatial activity index (SAI) 0.737; weighted spatial activity index (wSAI) 20.229, B. salicifolius (SAI 0.611; wSAI 14.804) and M. dictyophylla (SAI 0.586; wSAI 8.798); and (ii) Cx. quinquefasciatus: E. dysenterica - Protection (P) 71%, C. adamantium (P 61%) and B. salicifolius (P 60%). B. salicifolius leaves essential oil showed both insecticidal and repellent activity. Our results support the use of Cerrado plant essential oils at low concentrations as a promising alternative vector control strategy.

Potential Pharmaceutical Application of Endemic Plants: When will Sri Lanka Understand the Economic Value Chain?

Small molecules has been a main concern in the pharmaceutical industry for as long as they have existed. Enormous libraries of compounds have been collected and they in turn nurture drug discovery research. For example, big pharma, has in their compound libraries ranging from 500,000 to several million. Examining the drugs in the market, it is clear from where most are arriving: natural origin; out of the 1,328 new chemical entities approved as drugs between 1981 and 2016, only 359 were purely of synthetic origin. In the list of remaining ones, 326 were “biologics”, and 94 were vaccines. Importantly, 549 were from natural origin or arose motivated from natural compounds. Furthermore, anticancer compounds arising during the same period (1981–2014), only 23 were purely synthetic (Newman and Cragg, 2016). Natural origin can count for three categories: unaltered natural products; distinct mixture of natural products and natural product derivatives isolated from plants or other living organisms such as fungi, sponges, lichens, or microorganisms; and products modified through application of medicinal chemistry. There are many examples covering a wide spectrum of diseases: anticancer drugs such as docetaxel (Taxotere™), paclitaxel (Taxol™), vinblastine, podophyllotoxin (Condylin™), or etoposide; steroidal hormones such as progesterone, norgestrel, or cortisone; cardiac glycosides such as digitoxigenin; antibiotics like penicillin, streptomycin, and cephalosporins.

Computationally repurposed drugs and natural products against RNA dependent RNA polymerase as potential COVID-19 therapies

Repurposing of existing drugs and drug candidates is an ideal approach to identify new potential therapies for SARS-CoV-2 that can be tested without delay in human trials of infected patients. Here we applied a virtual screening approach using Autodock Vina and molecular dynamics simulation in tandem to calculate binding energies for repurposed drugs against the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We thereby identified 80 promising compounds with potential activity against SARS-Cov2, consisting of a mixture of antiviral drugs, natural products and drugs with diverse modes of action. A substantial proportion of the top 80 compounds identified in this study had been shown by others to have SARS-CoV-2 antiviral effects in vitro or in vivo, thereby validating our approach. Amongst our top hits not previously reported to have SARS-CoV-2 activity, were eribulin, a macrocyclic ketone analogue of the marine compound halichondrin B and an anticancer drug, the AXL receptor tyrosine kinase inhibitor bemcentinib. Our top hits from our RdRp drug screen may not only have utility in treating COVID-19 but may provide a useful starting point for therapeutics against other coronaviruses. Hence, our modelling approach successfully identified multiple drugs with potential activity against SARS-CoV-2 RdRp.

Using Porcine Jejunum Ex Vivo to Study Absorption and Biotransformation of Natural Products in Plant Extracts: Pueraria lobata as a Case Study.

Herbal preparations (HPs) used in folk medicine are complex mixtures of natural products (NPs). Their efficacy in vivo after ingestion depends on the uptake of the active ingredient, and, in some cases, their metabolites, in the gastrointestinal tract. Thus, correlating bioactivities measured in vitro and efficacy in vivo is a challenge. An extract of Pueraria lobata rich in different types of isoflavones was used to evaluate the capacity of viable porcine small intestine ex vivo to elucidate the absorption of HP constituents, and, in some cases, their metabolites. The identification and transport of permeants across the jejunum was monitored by liquid chromatography-mass spectrometry (LC-MS), combining targeted and untargeted metabolite profiling approaches. It was observed that the C-glycoside isoflavones were stable and crossed the intestinal membrane, while various O-glycoside isoflavones were metabolized into their corresponding aglycones, which were then absorbed. These results are consistent with human data, highlighting the potential of using this approach. A thorough investigation of the impact of absorption and biotransformation was obtained without in vivo studies. The combination of qualitative untargeted and quantitative targeted LC-MS methods effectively monitored a large number of NPs and their metabolites, which is essential for research on HPs.

Pterocarpus marsupium extract extends replicative lifespan in budding yeast.

As the molecular mechanisms of biological aging become better understood, there is growing interest in identifying interventions that target those mechanisms to promote extended health and longevity. The budding yeast Saccharomyces cerevisiae has served as a premier model organism for identifying genetic and molecular factors that modulate cellular aging and is a powerful system in which to evaluate candidate longevity interventions. Here we screened a collection of natural products and natural product mixtures for effects on the growth rate, mTOR-mediated growth inhibition, and replicative lifespan. No mTOR inhibitory activity was detected, but several of the treatments affected growth rate and lifespan. The strongest lifespan shortening effects were observed for green tea extract and berberine. The most robust lifespan extension was detected from an extract of Pterocarpus marsupium and another mixture containing Pterocarpus marsupium extract. These findings illustrate the utility of the yeast system for longevity intervention discovery and identify Pterocarpus marsupium extract as a potentially fruitful longevity intervention for testing in higher eukaryotes.

Metabolomic Characterization of a cf. Neolyngbya Cyanobacterium from the South China Sea Reveals Wenchangamide A, a Lipopeptide with In Vitro Apoptotic Potential in Colon Cancer Cells.

Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC50 = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues.

Synergistic Neuroprotective Effects of a Natural Product Mixture against AD Hallmarks and Cognitive Decline in Caenorhabditis elegans and an SAMP8 Mice Model

The study of different natural products can provide a wealth of bioactive compounds, and more interestingly, their combination can exert a new strategy for several neurodegenerative diseases with major public health importance, such as Alzheimer’s disease (AD). Here, we investigated the synergistic neuroprotective effects of a mixed extract composed of docosahexaenoic acid, Ginkgo biloba, D-pinitol, and ursolic acid in several transgenic Caenorhabditis elegans (C. elegans) and a senescence-accelerated prone mice 8 (SAMP8) model. First, we found a significantly higher survival percentage in the C. elegans group treated with the natural product mixture compared to the single extract-treated groups. Likewise, we found a significantly increased lifespan in group of C. elegans treated with the natural product mixture compared to the other groups, suggesting synergistic effects. Remarkably, we determined a significant reduction in Aβ plaque accumulation in the group of C. elegans treated with the natural product mixture compared to the other groups, confirming synergy. Finally, we demonstrated better cognitive performance in the group treated with the natural product mixture in both AD models (neuronal Aβ C. elegans strain CL2355 and the SAMP8 mice model), confirming the molecular results and unraveling the synergist effects of this combination. Therefore, our results proved the potential of this new natural product mixture for AD therapeutic strategies.

Neuroprotective Natural Products for Alzheimer's Disease.

Alzheimer’s disease (AD) is the number one neurovegetative disease, but its treatment options are relatively few and ineffective. In efforts to discover new strategies for AD therapy, natural products have aroused interest in the research community and in the pharmaceutical industry for their neuroprotective activity, targeting different pathological mechanisms associated with AD. A wide variety of natural products from different origins have been evaluated preclinically and clinically for their neuroprotective mechanisms in preventing and attenuating the multifactorial pathologies of AD. This review mainly focuses on the possible neuroprotective mechanisms from natural products that may be beneficial in AD treatment and the natural product mixtures or extracts from different sources that have demonstrated neuroprotective activity in preclinical and/or clinical studies. It is believed that natural product mixtures or extracts containing multiple bioactive compounds that can work additively or synergistically to exhibit multiple neuroprotective mechanisms might be an effective approach in AD drug discovery.

Validation of Natural Cosmetic Resources Containing EtOH Extracts of Chrysanthemum indicum and Cymbopogon cirtratus by the Simultaneous Analysis of Their Marker Compounds Using High Performance Liquid Chromatography-Diode Array Detector

Purpose: Recently, the demand for natural extracts and naturally derived ingredients from core raw materials has increased in the cosmetic industry, but their manufacturing and quality control standards are not sufficiently established. This study aims to standardize the compositions of marker compounds from natural cosmetics using ethanol extracts of Chrysanthemum indicum (CI) and Cymbopogon cirtratus (CC). The method is then validated. Methods: In liquid chromatography (LC)/mass spectrometry, astragalin and p -coumaric acid were determined as the marker compounds for quantitative analysis. The performances (linearity, accuracy, and precision) of these two marker components were simultaneously analyzed in a mixture of both natural products using high-performance liquid chromatography with a diode array detector (HPLC-DAD). Results: The marker compounds of CI and CC in the extracts were determined as astragalin and p -coumaric acid, respectively. The detected marker compounds from the CI and CC showed significant linearity (R2≥0.9999). The astragalin and p -coumaric acid markers achieved limits of detection of 1.20 and 0.07 ng/mL, respectively, and limits of quantification of 3.59 and 0.22 ng/mL, respectively. The marker concentrations were 0.24 μg/mL in CI and 1.55 μg/mL in CC. Conclusion: This study suggests that the developed method may be an important basic data for the manufacturing and quality control of natural cosmetic.

An Integrated Strategy for the Detection, Dereplication, and Identification of DNA-Binding Biomolecules from Complex Natural Product Mixtures.

A fundamental factor in natural product drug discovery programs is the necessity to identify the active component(s) from complex chemical mixtures. Whereas this has traditionally been accomplished using bioassay-guided fractionation, we questioned whether alternative techniques could supplement and, in some cases, even supplant this approach. We speculated that a combination of ligand-fishing methods and modern analytical tools (e.g., LC-MS and online natural product databases) offered a route to enhance natural product drug discovery. Herein, a candidate solution referred to as the lickety-split ligand-affinity-based molecular angling system (LLAMAS) is described. This approach utilizes an ultrafiltration-based LC-PDA-MS/MS-guided DNA-binding assay in combination with the (i) Global Natural Products Social Molecular Networking, (ii) Dictionary of Natural Products, and (iii) SciFinder platforms to identify DNA binders in complex chemical mixtures. LLAMAS was initially vetted in tests using known small-molecule DNA binders and then optimized to a 96-well plate-based format. A set of 332 plant samples used in traditional Chinese medicine was screened for DNA-binding activity with LLAMAS, resulting in the identification of seven DNA-binding molecules, including berberine (12), palmatine (13), coptisine (14), fangchinoline (15), tetrandrine (16), daurisoline (17), and dauricine (18). These results demonstrate that LLAMAS is an effective natural product discovery platform for the efficient identification and dereplication of DNA-binding molecules from complex mixtures.

Suppression of Inflammation, Osteoclastogenesis and Bone Loss by PZRAS Extract.

Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPStreated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.

Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients

Novel antimicrobials are urgently needed to combat drug-resistant bacteria and to overcome the inherent difficulties in treating biofilm-associated infections. Studying plants and other natural materials used in historical infection remedies may enable further discoveries to help fill the antibiotic discovery gap. We previously reconstructed a 1,000-year-old remedy containing onion, garlic, wine, and bile salts, known as ‘Bald’s eyesalve’, and showed it had promising antibacterial activity. In this current paper, we have found this bactericidal activity extends to a range of Gram-negative and Gram-positive wound pathogens in planktonic culture and, crucially, that this activity is maintained against Acinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes in a soft-tissue wound biofilm model. While the presence of garlic in the mixture can explain the activity against planktonic cultures, garlic has no activity against biofilms. We have found the potent anti-biofilm activity of Bald’s eyesalve cannot be attributed to a single ingredient and requires the combination of all ingredients to achieve full activity. Our work highlights the need to explore not only single compounds but also mixtures of natural products for treating biofilm infections and underlines the importance of working with biofilm models when exploring natural products for the anti-biofilm pipeline.

Extraction of Individual Spectra from Mixture Data Based on High-Resolution 13C-13C NMR Correlation Spectrum and DECODE Procedure.

In NMR analysis of complex organic molecules, low natural abundance of 13C and the low resolution of two-dimensional (2D) experiments are significant difficulties. Also challenging is the analysis of a mixture spectrum without separation, which has been limited to simple molecules. Through nonuniform sampling using modified heteronuclear multiple bond correlationcombined with indirect covariance, a high-resolution13C-13C correlation spectrum was obtained with 1H sensitivity. Built on the thus-obtained 13C-13C connectivities, deconvolution of the mixture spectra was achieved through a new signal-processing procedure, termed DECODE, tailored to the indirect covariance eigendecomposition. When applied to a complex natural product mixture of rotenone and brucine with many quaternary carbons, the method resolved very close carbon peaks and extracted clean individual spectra. Essentially providing molecule-wide 13C connectivities for complex molecules from 1H-detected 2D spectra, our approach should prove useful in many areas of NMR analysis.

Investigation of memory-enhancing botanical mixture and their isolated compounds for inhibition of amyloid-β and tau aggregation

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the abnormal assembly of amyloid-β (Aβ) and tau aggregates in the brain. When Aβ and tau proteins misfold, progressive brain cell death, synaptic loss, atrophy, and cognitive decline are observed. Here, we report that the memory-enhancing botanical natural product mixture, HX106N, efficiently inhibits formation of Aβ oligomers and fibrils and aggregation of tau. HX106N is a botanical mixture extract of Dimocarpus longan, Liriope platyphylla, Salvia miltiorrhiza and Gastrodia elata. In previous clinical studies, HX106N showed increased working memory performances of individuals of subjective memory complaints. However, the drug mechanism and responsible ingredients of HX106N has been unclear yet. In this study, we expanded the investigation of the drug mode of action to the single chemical level by identifying four active components of HX106N, among 14 isolated molecules, with significant inhibitory function against Aβ aggregation. We found that salvianolic acids A, B, E and rosmarinic acid, isolated from the botanical mixture, have potency to inhibit the protein misfolding.

Chemometrics-Assisted Identification of Anti-Inflammatory Compounds from the Green Alga Klebsormidium flaccidum var. zivo.

The green alga Klebsormidium flaccidum var. zivo is a rich source of proteins, polyphenols, and bioactive small-molecule compounds. An approach involving chromatographic fractionation, anti-inflammatory activity testing, ultrahigh performance liquid chromatography-mass spectrometry profiling, chemometric analysis, and subsequent MS-oriented isolation was employed to rapidly identify its small-molecule anti-inflammatory compounds including hydroxylated fatty acids, chlorophyll-derived pheophorbides, carotenoids, and glycoglycerolipids. Pheophorbide a, which decreased intracellular nitric oxide production by inhibiting inducible nitric oxide synthase, was the most potent compound identified with an IC50 value of 0.24 µM in lipopolysaccharides-induced macrophages. It also inhibited nuclear factor kappaB activation with an IC50 value of 32.1 µM in phorbol 12-myristate 13-acetate-induced chondrocytes. Compared to conventional bioassay-guided fractionation, this approach is more efficient for rapid identification of multiple chemical classes of bioactive compounds from a complex natural product mixture.

The Effect of Mixture of Natural Products As Salivary Substitutes in Treatment Of Xerostomia

the Effect of Mixture of Natural Products As Salivary Substitutes in Treatment Of Xerostomia