Objectives: Baseline presence of nonstructural protein 5A (NS5A) resistance-associated variants can attenuate the efficacy of new direct-acting antivirals. A potential method to attain the higher efficacy would be to screen for NS5A polymorphisms prior to the initiation of therapy and to adjust the treatment length based on the test results. However, baseline testing adds additional costs and it is unclear whether this would represent a high value strategy for chronic hepatitis C in China. Methods: A hybrid model compared 1) standard 12-weeks treatment (no testing), 2) shortened 8-weeks treatment (no testing), and 3) baseline testing with 12-/8-weeks treatment for those with/without NS5A polymorphisms from a lifetime Chinese health care payer perspective. All model inputs were retrieved from clinical trials and publically available literature. And sensitivity analyses were also conducted to assess the impact of uncertainty. Results: Baseline testing was associated with overall increase in total health care cost of USD 13.50 and in QALYs of 0.002 compared with standard 12-weeks treatment (no testing), yielded in an ICER of USD 6750/QALY gained. Scenario analyses suggested that shortened 8-weeks treatment (no testing) was found to be lower costs and great QALYs compared with other two strategies when the sustained virologic response (SVR) rate increased to 95%. Sensitivity analyses indicated that the results were robust. Conclusions: Our results suggest prior assessment of NS5A sensitivity followed by optimizing treatment duration was an economic strategy. In addition, shortened 8-weeks treatment (no testing) was shown to be dominant with the SVR rate increased to 95%.
The leaves of Neolamarckia cadamba (NC) (Roxb.) Bosser (family: Rubiaceae) are traditionally used to treat breast cancer in Malaysia; however, this traditional claim is yet to be scientifically verified. Hence, this study was aimed to evaluate the anticancer effect of NC leaves' ethanol extract against breast cancer cell line (MCF-7 cells) using an in vitro cell viability, cytotoxicity, and gene expression assays followed by the gas chromatography analysis to further confirm active principles. Results revealed 0.2 mg/ml as the half maximal inhibitory concentration (IC50) against MCF-7. The extract exerted anticancer effect against MCF-7 cells in a dose- and time-dependent manner. The cell cycle assay showed that the extract arrested MCF-7 cells in the G0/G1 phase, and apoptosis was observed after 72 h by the Annexin-V assay. The gene expression assay revealed that the cell cycle arrest was associated with the downregulation of CDK2 and subsequent upregulation of p21 and cyclin E. The extract induced apoptosis via the mediation of the mitochondrial cell death pathways. A chromatography analysis revealed the contribution of D-pinitol and myo-inositol as the two major bioactive compounds to the activity observed. Overall, the study demonstrated that NC leaves' ethanol extract exerts anticancer effect against MCF-7 human breast cancer cells through the induction of apoptosis and cell cycle arrest, thereby justifying its traditional use for the treatment of breast cancer in Malaysia.
Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.
K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.
Allergic diseases are a global health burden with increasing prevalence. Side effects of available medications (antihistamines and steroids), lack of patients' perceived effectiveness and high cost of biologic therapies (omalizumab) are challenges to the clinical management of allergic diseases. As allergy symptoms persist for a long time, complementary and alternative medicine (CAM) such as propolis may be considered a potential prophylactic or therapeutic option to avoid long-term medication use. Propolis is a natural resinous substance produced by bees. Although propolis is well known to possess antioxidant, antimicrobial, and anticancer properties, its anti-allergic potential is not fully explored. Several preclinical studies demonstrated the therapeutic effects of propolis extracts against allergic inflammation, asthma, allergic rhinitis, atopic dermatitis, and food allergy, which may be partly attributed to their inhibitory effects on the activation of mast cells and basophils. Clinically, the consumption of propolis as a supplement or an adjunct therapy is safe and attenuates various pathological conditions in asthma. Such an approach may be adopted for atopic dermatitis and allergic rhinitis. Although flavonoids (chrysin, kaempferol, galangin, and pinocembrin) and cinnamic acid derivatives (artepillin C and caffeic acid phenethyl ester) can contribute to the anti-allergic activities, they may not be present in all propolis samples due to variations in the chemical composition. Future studies should relate the anti-allergic activity of propolis with its chemical contents. This mini-review summarizes and discusses existing preclinical and clinical studies reporting the anti-allergic activities of propolis to provide insights into its potential applications in allergic diseases.
Background: With the increased availability of safe antiretroviral therapy (ART) in recent years, achieving optimal adherence and patient retention is becoming the biggest challenge for people living with HIV (PLWH). Care retention is influenced by several socioeconomic, socio-cultural, and government policies during the COVID-19 pandemic. Therefore, we aim to explore barriers and facilitators to adherence to ART among PLWH in Pakistan in general and COVID-19 pandemic related in particular. Methods: Semi-structured interviews were conducted among 25 PLWH from December 2020 to April 2021 in the local language (Urdu) at the ART centre of Pakistan Institute of Medical Sciences, Islamabad, Pakistan. Interviews were audio-recorded in the local Urdu language, and bilingual expert (English, Urdu) transcribed verbatim, coded for themes and sub-themes, and analyzed using a phenomenological approach for thematic content analysis. Results: Stigma and discrimination, fear of HIV disclosure, economic constraints, forgetfulness, religion (Ramadan, spiritual healing), adverse drug reactions, lack of social support, alternative therapies, and COVID-19-related lock-down and fear of lesser COVID-19 care due to HIV associated stigma were identified as barriers affecting the retention in HIV care. At the same time, positive social support, family responsibilities, use of reminders, the beneficial impact of ART, and initiation of telephone consultations, courier delivery, and long-term delivery of antiretrovirals during COVID-19 were identified as facilitators of HIV retention. Conclusion: Improving adherence and retention is even more challenging due to COVID-19; therefore, it requires the integration of enhanced access to treatment with improved employment and social support. HIV care providers must understand these reported factors comprehensively and treat patients accordingly to ensure the continuum of HIV care. A coordinated approach including different stakeholders is required to facilitate patient retention in HIV care and consequently improve the clinical outcomes of PLWH.
Chamomile (Matricaria chamomilla L.) is a traditional medicinal plant used to treat hay fever, inflammation, muscle spasms, menstrual disorders, insomnia ulcers, wounds, gastrointestinal disorders, rheumatic pain, and hemorrhoids. Dried chamomile flowers have a longer shelf life and the dried extract in form of powder offers much flexibility for new therapeutic formulations as it could be used as a replacement for liquid extract and serve as a shelf-stable ingredient in new applications. This study aims to determine the effect of drying methods, i.e., convection oven-drying at 45 °C, freeze-drying at -50°C, and spray-drying at 140°C at 10.5 and 12 ml/min, respectively) on powder yield, physicochemical properties (moisture content, water activity, and color attributes), and total polyphenol content of chamomile extract powder. Our findings showed that spray-drying conducted at 140°C, 12 ml/min resulted in the lowest yield of powder (16.67%) compared to convection oven-drying (90.17%) and freeze-drying (83.24%). Decreasing the feed flow rate to 10.5 ml/min during spraying caused an increase in powder yield to 26.99%. The moisture content of spray-dried chamomile extract powder obtained at 140°C, 10.5 ml/min was higher (11.00%) compared to that of convection oven-dried (8.50%) and freeze-dried (7.50%). Both convection oven-dried and freeze-dried chamomile extract powder displayed no significant difference (p > 0.05) in moisture content. The higher feed flow rate (12 ml/min) in spray-drying also led to an increase in the moisture content of chamomile extract powder to 12.00%. The higher residual moisture found in the spray-dried samples resulted in partial agglomeration of particles. In terms of water activity, freeze-dried chamomile extract powder was found to have the highest water activity (0.63) compared to that of convection oven-dried (0.52), spray-dried at 140°C, 10.5 ml/min (0.57), and spray-dried at 140°C, 12 ml/min (0.58). Spray-dried and freeze-dried chamomile extract powder with high moisture content and water activity could be highly susceptible to microbial growth. In terms of color attributes, higher drying temperature in spray-drying led to darker, redder, and more yellowish chamomile extract powder that could be caused by heat-induced Maillard reaction and caramelization. Since lower drying temperature was used in both convection oven-drying and freeze-drying, both convection oven-dried (56.94 mg GAE/g powder) and freeze-dried chamomile extract powder (55.98 mg GAE/g powder) were found to have higher total polyphenol content compared to those of spray-dried (42.79-46.79 mg GAE/g powder). The present findings allow us to understand the effect of drying methods on the properties of chamomile extract powder and provide a better drying option to dry chamomile extract. Due to higher powder yield with ideal powder properties such as low moisture content and water activity, desirable color, and high total polyphenol content obtained from convection oven-drying, convection oven-drying was a better option than freeze-drying and spray-drying for drying chamomile extract.
Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 μg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.
ABT-199 (venetoclax) is the first-in-class selective B-cell lymphoma 2 (BCL2) inhibitor, which is known to be ineffective towards liver cancer cells. Here, we investigated the efficacy and the underlying molecular processes of the sensitization effect of kaempferol isolated from persimmon leaves (KPL) on the ABT-199-resistant HepG2 cells. The effects of various doses of KPL coupled with ABT-199 on the proliferation of HepG2 cells and on the H22 liver tumor-bearing mouse model were examined, as well as the underlying mechanisms. Our findings showed that ABT-199 alone, in contrast to KPL, had no significant impact on hepatoma cell growth, both in vitro and in vivo. Interestingly, the combination therapy showed significantly higher anti-hepatoma efficacy. Mechanistic studies revealed that combining KPL and ABT-199 may promote both early and late apoptosis, as well as decrease the mitochondrial membrane potential in HepG2 cells. Western blot analysis showed that combination of KPL and ABT-199 significantly reduced the expression of the anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1, raised the expression of Bax and cleaved caspase 3, and enhanced cytochrome C release and Bax translocation. Therefore, KPL combined with ABT-199 has a potential application prospect in the treatment of hepatocellular carcinoma.
Background: Antibiotic resistance (ABR) is one of the major issues around the globe. Timely education and awareness of pharmacy students regarding the appropriate use of antibiotics, ABR, and antimicrobial stewardships are required. Methods: The present study was first conducted in 12 (public and private sector) universities among undergraduate pharmacy students (UGPS) (n = 414) irrespective of their study year through a validated questionnaire, and the insights of pharmacy teachers were taken through in-depth semi-structured interviews in the second phase. For the quantitative data, different statistical methods were used, and data were presented in tabulated form, whereas inductive thematic interpretation was used to categorize themes and derive conclusions from qualitative evidence. Results: The majority of the students were males (n = 223, 54%) with the mean age group 19-23 years, and 20 faculty members were interviewed with a mean duration of 15 min. Students have good knowledge about antibiotics use and the majority purchased antibiotics through prescription (n = 277, 66.9%) during the last month and strongly agreed to stop unnecessary household storage (n = 183 44.2%). Most of the students have heard the terminologies related to antimicrobial resistance through social media while unaware (n = 104, 25.1%) of a Pakistan national action plan against AMR (antimicrobial resistance). Overall, respondents have a somewhat good understanding of the ABR. Regular use of antibiotics without consultation of a physician can lead to ABR and some wrong answers were observed (162, 39.1%; p > 0.05). The majority of the students (n = 198, 47.8%) and teachers believe that the current pharmacy syllabus must be swiftly updated with the new subjects related to ABR and AMS (antimicrobial stewardship) in Pakistan. The UGPS have emphasized (n = 220, 53.1%; Median = 1, IQR = 2) establishing a link between academia and hospitals. The ABR issue has been highlighted by pharmacy faculty members, who have urged students to take practical efforts toward ABR and AMS knowledge. Conclusion: The UGPS knowledge related to ABR and AMS must be updated. Students at the undergraduate level must get training in order to encourage the sensible use of antibiotics. Courses on ABR and AMS should be included in present pharmacy curricula.
Background: Hypertension is a major risk factor for cardiovascular disease (CVD), which is the number one cause of global mortality. The potential use of natural products to alleviate high blood pressure has been demonstrated to exert a cardioprotective effect. Centella asiatica (L.) Urb. belongs to the plant family Apiaceae (Umbelliferae). It contains a high amount of triterpenoid and flavonoid that have antioxidant properties and are involved in the renin-angiotensin-aldosterone system which is an important hormonal system for blood pressure regulation. Objective: This study aimed to investigate the effects of C. asiatica ethanolic extract on blood pressure and heart in a hypertensive rat model, which was induced using oral N(G)-nitro-l-arginine methyl ester (l-NAME). Methods: Male Sprague-Dawley rats were divided into five groups and were given different treatments for 8 weeks. Group 1 only received deionized water. Groups 2, 4, and 5 were given l-NAME (40 mg/kg, orally). Groups 4 and 5 concurrently received C. asiatica extract (500 mg/kg, orally) and captopril (5 mg/kg, orally), respectively. Group 3 only received C. asiatica extract (500 mg/kg body weight, orally). Systolic blood pressure (SBP) was measured at weeks 0, 4, and 8, while serum nitric oxide (NO) was measured at weeks 0 and 8. At necropsy, cardiac and aortic malondialdehyde (MDA) contents, cardiac angiotensin-converting enzyme (ACE) activity, and serum level of brain natriuretic peptide (BNP) were measured. Results: After 8 weeks, the administrations of C. asiatica extract and captopril showed significant (p < 0.05) effects on preventing the elevation of SBP, reducing the serum nitric oxide level, as well as increasing the cardiac and aortic MDA content, cardiac ACE activity, and serum brain natriuretic peptide level. Conclusion: C. asiatica extract can prevent the development of hypertension and cardiac damage induced by l-NAME, and these effects were comparable to captopril.
Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol-nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague-Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol-PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young's modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol-PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.
Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.
Parallel to the growing use of kratom, there is a wealth of evidence from self-report, preclinical, and early clinical studies on therapeutic benefits of its alkaloids in particular for treating pain, managing substance use disorder, and coping with emotional or mental health conditions. On the other hand, there are also reports on potential health risks concerning kratom use. These two aspects are often discussed in reviews on kratom. Here, we aim to highlight specific areas that are of importance to give insights into the mechanistic of kratom alkaloids pharmacological actions. This includes their interactions with drug-metabolizing enzymes and predictions of clinical drug-drug interactions, receptor-binding properties, interactions with cellular barriers in regards to barrier permeability, involvement of membrane transporters, and alteration of barrier function when exposed to the alkaloids.
Hepatitis is an inflammatory disease of the liver and is considered one of the leading causes of death worldwide. Due to its scavenging activity, Punica granatum may be used for the treatment and prevention of liver diseases. The current study investigated the protective mechanism underlying the effects of pomegranate against a rat model of carbon tetrachloride-induced liver injury. Intraperitoneal injection of CCl4 resulted in liver inflammation, oxidative stress, and accumulation of lipid in hepatocytes. CCl4 induced a downregulation of superoxide dismutase (SOD), glutathione (GSH), and melonaldehyde (MDA). Pomegranate protection was assessed in terms of biochemical parameters, histopathology, and immunohistochemistry. Promegranate administration decreased inflammation, elevated serum enzymes and ROS production, and countered the debilitating effects caused by CCl4. In addition, CCl4-induced histological changes were absent in the crude pomegranate extract group, which also enhanced the scavenging activity of reactive oxygen species by enhancing the antioxidant defense mechanism as confirmed by detecting MDA, SOD, and GSH expressions. The migration of CD68+ macrophages was halted at the injured area of the central vein and the number of macrophages was reduced to the normal control by the crude extract compared to the positive control silymarin group. Likewise, protective effects of ethylacetate and the aqueous fraction of the crude extract were also observed. However, the butanol and n-hexane fractions displayed increased levels of ALT, AST, and ALP as compared to silymarin. About 25% damage to hepatocytes was observed in the butanol and n-hexane group by histopathological examination, which is a little better compared to the CCl4-treated group. The crude extract and its ethyl acetate and aqueous fractions may be accountable for the hepatoprotective potential of Punica granatum, which was further confirmed by in vivo experiments. Together, these findings confirm that pomegranate exerts hepatoprotective activity against CCl4-induced oxidative stress and liver damage.
Atherosclerosis poses serious health problems and increases the risk of various cardiovascular diseases, including myocardial infarction, heart failure, ischemic stroke, and peripheral arterial disease. Atherosclerosis patients require long-term medications to prevent complications, some of which are costly and may result in unwanted adverse reactions. Natural products have emerged as potential sources of bioactive compounds that provide health benefits in cardiovascular diseases. Increased inflammation and vascular remodeling have been associated with atherosclerosis pathogenesis. The molecules involved in signaling pathways are considered valuable targets for new treatment approaches. Therefore, this review aimed to summarize the available evidence of the anti-inflammatory effects of thymoquinone, the major active compound isolated from Nigella sativa L., via inflammatory signaling pathways in atherosclerosis. Specifically, nuclear factor-κB and mitogen-activated protein kinase signaling pathways were considered. Furthermore, the potential toxic effects elicited by thymoquinone were addressed. These findings suggest a potential role of thymoquinone in managing atherosclerosis, and further studies are required to ascertain its effectiveness and safety profile.
Background: The effects of coffee consumption on hepatic outcomes are controversial. This study investigated the associations between coffee consumption and the incidence of non-alcoholic fatty liver disease (NAFLD) in the general population and the reduction of liver fibrosis among patients with NAFLD. Methods: The study consisted of two parts: an umbrella review and a systematic review and meta-analysis (SRMA). The searches for each part were performed separately using PubMed, EMBASE, Cochrane, Scopus, and CINAHL databases. All articles published up to September 2021 were reviewed. To be eligible, studies for the umbrella review were required to report outcomes that compared the risks of NAFLD in the general population and/or liver fibrosis in patients with NAFLD who did and did not drink coffee. Our SRMA included primary studies reporting the effects of coffee consumption on NAFLD-related outcomes. The outcomes were pooled using a random-effects model and reported in both qualitative and quantitative terms (pooled risk ratio, odds ratio, and weighted mean difference). Results: We identified four published SRMAs during the umbrella review. Most studies showed that individuals in the general population who regularly drank coffee were significantly associated with a lower NAFLD incidence than those who did not. Our SRMA included nine studies on the effects of coffee consumption on NAFLD incidence. Pooled data from 147,875 subjects showed that coffee consumption was not associated with a lower NAFLD incidence in the general population. The between-study heterogeneity was high (I 2, 72-85%). Interestingly, among patients with NAFLD (5 studies; n = 3,752), coffee consumption was significantly associated with a reduction in liver fibrosis (odds ratio, 0.67; 95% CI, 0.55 to 0.80; I 2, 3%). There were no differences in the coffee consumption of the general population and of those with NAFLD (4 studies; n = 19,482) or by patients with no/mild liver fibrosis and those with significant fibrosis (4 studies; n = 3,331). Conclusions: There are contrasting results on the effects of coffee on NAFLD prevention in the general population. Benefits of coffee consumption on liver fibrosis were seen among patients with NAFLD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226607, identifier CRD42021226607.