Anti-inflammatory Constituents Research Articles

Clinical rationale for dietary lutein supplementation in long COVID and mRNA vaccine injury syndromes

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. High dietary intake of lutein is beneficial against eye disease, improves cardiometabolic health, protects from neurodegenerative diseases, and is beneficial for liver, kidney, and respiratory health. Lutein protects against oxidative and nitrosative stress, both of which play a major role in post-COVID and mRNA vaccination injury syndromes. Lutein is an important natural agent for therapeutic use against oxidative and nitrosative stress in chronic illnesses such as cardiovascular and neurodegenerative diseases and cancer. It can also potentially inhibit spike protein-induced inflammation. Rich dietary supplementation of lutein, naturally derived in non-biodegradable Extra Virgin Olive Oil (EVOO), can most optimally be used against oxidative and nitrosative stress during post-COVID and mRNA vaccination injury syndromes. Due to its high oleic acid (OA) content, EVOO supports optimal absorption of dietary lutein. The main molecular pathways by which the SARS-CoV-2 spike protein induces pathology, nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and activated protein (AP)-1, can be suppressed by lutein. Synergy with other natural compounds for spike protein detoxification is likely.

New Isoflavonoid and Anti-Inflammatory Constituents from Myristica elliptica var. simiarum

New Isoflavonoid and Anti-Inflammatory Constituents from Myristica elliptica var. simiarum

Polygala tenuifolia willd. Extract alleviates LPS-induced acute lung injury in rats via TLR4/NF-κB pathway and NLRP3 inflammasome suppression

BackgroundAcute lung injury (ALI) has received considerable attention in the field of critical care as it can lead to high mortality rates. Polygala tenuifolia, a traditional Chinese medicine with strong expectorant properties, can be used to treat pneumonia. Owing to the complexity of its composition, the main active ingredient is not yet known. Thus, there is a need to identify its constituent compounds and mechanism of action in the treatment of ALI using advanced technological means. PurposeWe investigated the anti-inflammatory mechanism and constituent compounds with regard to the effect of P. tenuifolia Willd. extract (EPT) in lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. MethodsThe UHPLC-Q-Exactive Orbitrap MS technology was used to investigate the chemical profile of EPT. Network pharmacology was used to predict the targets and pathways of action of EPT in ALI, and molecular docking was used to validate the binding of polygalacic acid to Toll-like receptor (TLR) 4. The main compounds were determined using LC-MS. A rat model of LPS-induced ALI was established, and THP-1 cells were stimulated with LPS and adenosine triphosphate (ATP) to construct an in vitro model. Pathological changes were observed using hematoxylin and eosin staining, Wright-Giemsa staining, and immunohistochemistry. The expression of inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1β, IL-6, and iNOS) was determined using enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The LPS + ATP-induced inflammation model in THP-1 cells was used to verify the in vivo experimental results. ResultsNinety-nine compounds were identified or tentatively deduced from EPT. Using network pharmacology, we found that TLR4/NF-κB may be a relevant pathway for the prevention and treatment of ALI by EPT. Polygalacic acid in EPT may be a potential active ingredient. EPT could alleviate LPS-induced histopathological lung damage and reduce the wet/dry lung weight ratio in the rat model of ALI. Moreover, EPT decreased the white blood cell and neutrophil counts in the bronchoalveolar lavage fluid and decreased the expression of genes and proteins of relevant inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1β, IL-6, and iNOS) in lung tissues. It also increased the expression of endothelial-type nitric oxide synthase expression. Western blotting confirmed that EPT may affect TLR4/NF-κB and NLRP3 signaling pathways in vivo. Similar results were obtained in THP-1 cells. ConclusionEPT reduced the release of inflammatory factors by affecting TLR4/NF-κB and NLRP3 signaling pathways, thereby attenuating the inflammatory response of ALI. Polygalacic acid is the likely compounds responsible for these effects.

Identification of Xuanfei Baidu granule constituents by liquid chromatography-quadruple-time-of-flight-mass spectrometry and its anti-inflammatory active constituents using a lipopolysaccharide-induced RAW264.7 cell model.

The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule.

A New Homoisoflavonoid and Anti-Inflammatory Constituents from Polygonatum alte-lobatum

A New Homoisoflavonoid and Anti-Inflammatory Constituents from Polygonatum alte-lobatum

New Phenanthrenoid Dimer Derivative and Anti-Inflammatory Constituents from Juncus effusus var. decipiens

New Phenanthrenoid Dimer Derivative and Anti-Inflammatory Constituents from Juncus effusus var. decipiens

Fatty acids in Plantago asiatica seeds are responsible for the production of the pro-inflammatory mediator nitric oxide

Background: Plantago asiatica L. (Plantaginaceae) commonly grows in East Asia, with its seeds (Shazenshi), having been used as diuretic and anti-inflammatory drugs in traditional Japanese medicine. It is not known which constituents of P. asiatica seeds elicit the anti-inflammatory effects, such as reduced expression of the inducible nitric oxide synthase (iNOS) in interleukin (IL)-1β-treated hepatocytes which leads to a reduction in the pro-inflammatory mediator nitric oxide (NO). Objective: To identify the anti-inflammatory constituents of P. asiatica seeds, the anti-inflammatory activity of purified constituents was determined by assaying NO production in IL-1β-treated hepatocytes. Methods: P. asiatica seeds were extracted with 50% methanol and successively fractionated into three crude fractions with ethyl acetate (EtOAc) and n-butanol. The compounds were methylated and analyzed by gas chromatography–mass spectrometry (GC–MS). Primary cultured rat hepatocytes were prepared by collagenase perfusion, and P. asiatica seed extract (PASE), a fraction, or a compound was added to the culture medium with IL-1β and incubated at 37 °C. Potency of each fraction was determined by the Griess method for measuring the levels of nitrite in the medium. Results: PASE suppressed IL-1β-induced NO production without showing cytotoxicity, and an EtOAc-soluble fraction of PASE significantly inhibited NO production. GC–MS analysis detected 26 distinct fatty acids as their methyl esters in this fraction. Among them, three unsaturated fatty acids (linoleic, oleic, and α-linolenic acids) and palmitic acid were abundant. These unsaturated fatty acids are known to reduce NO levels. In contrast, acteoside and aucubin, which are thought to be present in the n-butanol-soluble fraction, showed only a low level of NO production suppression. Conclusion: The EtOAc-soluble fraction of PASE included many fatty acids, which may suppress the production of NO. The results imply that the anti-inflammatory activity of P. asiatica seeds may be produced by three unsaturated fatty acids. Because the fatty acids are abundant in the seeds of medicinal plants, they are likely to contribute to anti-inflammatory activity of the seeds. Keywords: Plantain seed, polyunsaturated fatty acid, Kampo medicine, hepatocyte, nitric oxide.

TEMPORARY REMOVAL: Research progress and considerations on oral rehydration therapy for the prevention and treatment of severe burn shock: A narrative review

Severe burns are an important cause of life-threatening situations, whether in times of peace or war. Shock represents a critical complication during the early stages of burn injury and is a significant contributor to mortality and long-term disability. Effective fluid resuscitation is a crucial intervention for preventing and treating shock, and prompt administration is paramount. In numerous instances, prompt initiation of intravenous fluid resuscitation proves challenging and research indicates that resuscitation errors remain a critical contributor to the mortality of injured patients. Hence, it is imperative to explore a more expedient and efficacious non-invasive method for fluid resuscitation that can serve as a fundamental basis for the subsequent treatment of such individuals. There has been extensive research recently on the utilisation of oral rehydration, which exhibits vast potential for application in austere settings. This paper summarizes the historical development and research progress in oral rehydration therapy, briefly discusses the pathogenesis of burns, summarizes the characteristics of burn fluid resuscitation and discusses the application status of oral rehydration therapy in the early anti-shock treatment of burns. It aims to explore an effective fluid resuscitation method suitable for special conditions and provides ideas for improving the level of treatment for shock in peacetime and wartime. Oral rehydration therapy is generally considered safe; however, there are potential complications to be aware of. These include gastrointestinal discomfort such as diarrhoea, vomiting, and abdominal discomfort, particularly when the rehydration rate is too fast or there are preexisting gastrointestinal issues in the patient. Furthermore, it is important to note that oral rehydration therapy may not be appropriate for individuals suffering from gastrointestinal tract impairments. Therefore, when administering oral rehydration therapy, it is imperative for the physician to carefully assess the patient’s condition and closely monitor their response and tolerance. Based on a comprehensive review of research in relevant fields, we carefully present the following provisional guidelines for oral rehydration therapy in burn patients. It is critical to emphasize that, despite these guidelines being intended to inform clinical practice, they should be applied with caution due to the lack of robust clinical evidence. Implementation should either be cautious, considering the specifics of the patient’s condition, or conducted under the supervision of healthcare professionals. Additionally, these guidelines should be dynamically adjusted in response to the unique circumstances and evolving condition of each patient: ① Initiation timing: Start as soon as possible, and the ideal start time is usually within 6 h after injury. ② Rate of application: Employing a fractional administration approach, wherein small quantities of approximately 150–250 millilitres are provided for each instance and the initial fluid rate of oral rehydration can be simplified to 100 mL/kg/24 h. ③ Composition combination: In addition to essential salts and glucose, the oral rehydration solution can incorporate various anti-inflammatory and cellular protection constituents such as pyruvate, vitamins, teprenone or glutamine.

The power of Punica granatum: A natural remedy for oxidative stress and inflammation; a narrative review

Ethnopharmacological relevancePomegranate 'Punica granatum' offers multiple health benefits, including managing hypertension, dyslipidemia, hyperglycemia, insulin resistance, and enhancing wound healing and infection resistance, thanks to its potent antioxidant and anti-inflammatory properties. It has been symbolized by life, health, femininity, fecundity, and spirituality. Aim of the studyAlthough laboratory and animal studies have been conducted on the healing effects of pomegranate, there needs to be a comprehensive review on its anti-oxidative and anti-inflammatory effects in chronic disorders. We aim to provide a comprehensive review of these effects based on in-vitro, in-vivo, and clinical studies conducted in managing various disorders. Materials and methodsA comprehensive search of in-vitro, in-vivo, and clinical findings of pomegranate and its derivatives focusing on the highly qualified original studies and systematic reviews are carried out in valid international web databases, including Web of Science, PubMed, Scopus, and Cochrane Library. ResultsRelevant studies have demonstrated that pomegranate and its derivatives can modulate the expression and activity of several genes, enzymes, and receptors through influencing oxidative stress and inflammation pathways. Different parts of pomegranate; roots, bark, blossoms, fruits, and leaves contain various bioactive compounds, such as polyphenols, flavonoids, anthocyanins, and ellagitannins, that have preventive and therapeutic effects against many disorders such as cardiovascular diseases, diabetes, neurological diseases, and cancers without any serious adverse effects. ConclusionsMost recent scientific evidence indicates that all parts of the pomegranate can be helpful in treating a wide range of chronic disorders due to its anti-oxidative and anti-inflammatory activities. Since the safety of pomegranate fruit, juice, and extracts is established, further investigations can be designed by targeting its active antioxidant and anti-inflammatory constituents to discover new drugs.

Label-free Raman imaging for screening of anti-inflammatory function food

Natural bioactive compounds and plant constituents are considered to have a positive anti-inflammatory effect. This study aimed to establish a screening technique for anti-inflammatory function in foods based on label-free Raman imaging. A visible anti-inflammatory analysis method based on coherent anti-Stokes Raman scattering (CARS) was established with an LPS-induced RAW264.7 cell model. Dynamic changes in proteins and lipids were determined at laser pump light wavelengths of 2956 cm−1 and 2856 cm−1, respectively. The method was applied to a plant-based formula (JC) with anti-inflammatory activity. Q-TOF-MS and HPLC analyses revealed the main active constituents of JC as quercetin, kaempferol, l-glutamine, and sodium copper chlorophyllin. In in vitro and in vivo verification experiments, JC showed significant anti-inflammatory activity by regulating the TLR4/NF-κB pathway. In conclusion, this study successfully established a label-free and visible method for screening anti-inflammatory constituents in plant-based food products, which will facilitate the evaluation of functional foods.

Clinical rationale for dietary lutein supplementation in post COVID-19 and mRNA vaccine injury syndromes

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. High dietary intake of lutein is beneficial against eye disease, improves cardiometabolic health, protects from neurodegenerative diseases, and is beneficial for liver, kidney, and respiratory health. Lutein protects against oxidative and nitrosative stress, both of which play a major role in post-COVID and mRNA vaccination injury syndromes. Lutein is an important natural agent for therapeutic use against oxidative and nitrosative stress in chronic illnesses such as cardiovascular and neurodegenerative diseases and cancer. It can also potentially inhibit spike protein-induced inflammation. Rich dietary supplementation of lutein, naturally derived in non-biodegradable Extra Virgin Olive Oil (EVOO), can most optimally be used against oxidative and nitrosative stress during post-COVID and mRNA vaccination injury syndromes. Due to its high oleic acid (OA) content, EVOO supports optimal absorption of dietary lutein. The main molecular pathways by which the SARS-CoV-2 spike protein induces pathology, nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and activated protein (AP)-1, can be suppressed by lutein. Synergy with other natural compounds for spike protein detoxification is likely.

Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds.

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 μM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1β as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.

Anti-inflammatory constituents from a sea anemone-derived fungus Arthrinium arundinis MA30

In this study, preliminary field-sampling of bioactive fungal strains and bioassay-guided selection were conducted. A number of fungal strains were isolated from sea anemones along the northeastern coast of Badouzi, Keelung, Taiwan. Among them, Arthrinium arundinis MA30 showed significant anti-inflammatory activity and was thus selected for further chemical investigation. After a series of purification and isolation using different chromatographic techniques on the fermented products of A. arundinis MA30, thirty-one compounds were identified, five of which were previously unreported, including arthrinoic acid, hexylaconitic anhydride methyl ester, (3S,8R)-8-hydroxy-3-carboxy-2-methylenenonanoic acid, and arthripenoids G and H. These compounds were subjected to comprehensive spectroscopic data analysis. Of all the isolates, 1,3,5,6-tetrahydroxy-8-methylxanthone and arthripenoid C demonstrated the most distinctive inhibitory activities against nitric oxide production in mouse microglial BV-2 cells, with their respective inhibitory rates being 71% and 81% at 10 μM concentration, and their respective IC50 values were further determined to be 5.3 ± 0.6 and 1.6 ± 0.4 μM. These compounds showed no significant cytotoxicity, and curcumin was used as a positive control in this study.

Tree tomato: Underutilized vegetable for sustainable nutritional and economic security

Tree tomato is an underutilized high-value vegetable possessing high functional value to satisfy the needs of health-conscious people. Its fruits contain a diverse range of nutrients and bioactive compounds including vitamins, minerals, dietary fibers, polyphenols, anthocyanin, and carotenoids possessing potent nutraceutical properties. The presence of a wide range of bioactive compounds makes the fruits excellent antioxidative, antiproliferative, anti-inflammatory, and anti-obese food constituents. The crop has not yet been explored to full of its potential. Germplasm conservation strategies, hybridization, micropropagation, polyploidy, genetic engineering, genome editing etc. have been successfully utilized for the development of cultivars with improved traits in many crops and can be of help for the potential improvement of tree tomatoes. Nowadays, the changing food consumption patterns have resulted in an increased interest in the consumption of tree tomatoes. Advanced technologies for the development of value-added products with minimized losses, enhanced stability and bioavailability of bioactive compounds, and optimization of processes to preserve the functionality of the product need the attention of the scientific community. This paper summaries the functional characterization of major bioactive compounds, improvement strategies, and the effect of processing on quality traits along with futuristic approaches for the potential improvement of tree tomatoes.

Anti-Inflammatory Flavonoids from Agrimonia pilosa Ledeb: Focusing on Activity-Guided Isolation.

To elucidate the anti-inflammatory properties and constituents of Agrimonia pilosa Ledeb. (A. pilosa), a comprehensive investigation was conducted employing activity-guided isolation. The anti-inflammatory effects were evaluated through an in vitro nitric oxide (NO) assay on lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. Seven bio-active compounds with anti-inflammatory properties were successfully isolated from the butanol fraction and identified as follows: quercetin-7-O-β-d-rhamnoside (1), apigenin-7-O-β-d-glucopyranoside (2), kaempferol-7-O-β-d-glucopyranoside (3), quercetin (4), kaempferol (5), apigenin (6), and apigenin-7-O-β-d-glucuronide-6″-butylester (7). All isolated compounds showed strong NO inhibitory activity with IC50 values ranging from 1.4 to 31 µM. Compound 6 demonstrated the most potent NO inhibition. Compound 7, a rare flavonoid, was discerned as a novel anti-inflammatory agent, ascertained through its inaugural demonstration of nitric oxide inhibition. Subsequently, a comprehensive structure-activity relationship (SAR) analysis was conducted employing eight flavonoids derived from A. pilosa. The outcomes elucidated that flavones exhibit superior NO inhibitory effects compared to flavonols, and the aglycone form manifests greater potency in NO inhibition than the glycone counterpart. These results highlight A. pilosa as a promising source of effective anti-inflammatory agents and indicate its potential as a health-beneficial dietary supplement and therapeutic material.

Antioxidant and Anti-Inflammatory Constituents from Rhamnus crenata

Antioxidant and Anti-Inflammatory Constituents from Rhamnus crenata

Phytochemical Quantification and Characterization of Anti- Diabetic Potential of Polyherbal Formulation by FT-IR and GC-MS Analysis

The main objective of the present study was to develop and evaluate anti-diabetic potential of polyherbal formulation (PHF) using Nigella sativa, Cinnamomumverum, Allium sativum, Zingiberofficinale, Curcuma longa and Trigonellafoenumgraecum for management of diabetes. The PHF was investigated by advanced analytical techniques. The proximate analysis of PHF revealed all parameters were within the limits indicating no adulteration and contamination. In addition, gas chromatography-mass spectrometry (GC-MS) and Fourier transform-infrared (FT- IR) spectroscopy analysis showed the presence of bio-active phytochemicals including phenolic compounds, antioxidants, anti-inflammatory and anti-diabetic constituents that are good therapeutic potential for prevention and management of diabetes. The efficacy of PHF was evaluated by dividing into four groups (PHF 1.5 g, PHF 3.0 g, metformin 500 mg and placebo) of newly diagnosed type 2 diabetic patients for 90 consecutive days and monitored on a monthly basis. PHF 3.0 g dose showed a significantly higher anti-diabetic effect as compared to PHF 1.5 g while comparable results in relation to metformin 500 mg. The phytochemical characterization of PHF will ensure its quality and safety. Moreover, the anti-diabetic efficacy of PHF is comparable with anti-diabetic efficacy of metformin. PHF has the potential to achieve glycemic control in type 2 diabetic patients with a diabetic diet prescribed.

Integration of fingerprint-activity relationship and chemometric analysis to accurately screen Q-markers for the quality control of traditional Chinese medicine compound preparation: Jinlian Qingre granules as an example

This study aims to develop a comprehensive strategy that accurately screens and quantifies quality markers (Q-markers) by combining LC-MS metabolomics with fingerprint-effect relationships, chemometrics, and QAMS methods for the quality control in traditional Chinese medicine compound preparations (CMP). First, the chemical compositions in Jinlian Qingre granules (JQG) were analyzed and identified using ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Next, the HPLC fingerprint of JQG was established, and chemometrics were employed to evaluate JQG quality. Then, potential anti-inflammatory bioactive constituents were screened using a fingerprinting-effect relationship model utilizing partial least squares regression (PLSR) and a back propagation neural network optimized using a genetic algorithm (GA-BPNN). On this basis, Q-markers of JQG were determined and analyzed using quantitative analysis of multi-components by the single marker (QAMS) employing three components as reference substances (RS). 24 chemical constituents in JQG were characterized using UHPLC-HRMS. Twenty-four common peaks were assigned to the fingerprint. Six compounds, mangiferin, 2′'-O-beta-L-galactopyranosylorientin, orientin, veratric acid, vitexin, and harpagoside, identified from the common peaks associated with anti-inflammatory efficacy, could be used as Q-markers of JQG. The content determination results displayed no significant difference in the content of Q-markers in 20 batches of JQG samples measured using the external standard method and QAMS. Q-markers could be efficiently screened and determined by integrating multidisciplinary technologies. This comprehensive strategy could be beneficial for the thorough evaluation of CMP.

Cytotoxic and anti-inflammatory constituents from roots of Hypericum beanii and the antitumor potential under the view of cancer-related inflammation

Hypericum beanii, a traditional folk medicine plant, has been employed in the treatment of various inflammation-related diseases and has demonstrated promising potential as an herbal remedy for cancer. In this study, we isolated 29 compounds from the roots of H. beanii. We evaluated their cytotoxic effects on five human cancer cell lines, which revealed that the ethanol extract, along with compounds 4 and 14, exhibited significant cytotoxic activity. Additionally, we assessed their anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Our findings showed that the ethanol extract (IC50 = 7.41 ± 0.38 μg/mL), compound 4 (IC50 = 7.82 ± 0.42 μM), and compound 14 (IC50 = 3.05 ± 0.06 μM) displayed substantial anti-inflammatory activity. ELISA assays and qPCR analysis revealed that compounds 4 and 14 may exert their anti-inflammatory and antitumor effects by inhibiting the expression of iNOS, TNF-α, IL-1β, and IL-6 mRNA, shedding light on their role in cancer-related inflammation.

Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats.

Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1β, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.