Hawthorn Fruit’s Chemical Background for Reducing Liver Ailments

Extracts from hawthorn are beneficial against cancer, fibrosis, inflammation, fat deposition, and hepatic toxicity. Hawthorn extracts may have their pharmacological effects primarily from decreased hepatic oxidative stress, which inhibits excessive reactive oxygen species (ROS) attack and subsequently promotes the recovery of hepatocellular function. Its modulatory role in hepatic pathologic conditions also involves the regulation of AMPK, NIK, apoptosis, cholesterol metabolism, HSC activation, cell cycle arrest, and autophagy by hawthorn extracts. Even though extensive research is required to determine the plant’s safety, efficacy, and mode of action against liver diseases, hawthorn extracts may be safe and promising in the treatment of hepatic disorders.

The liver is a vital organ that removes hazardous substances from the body and filters blood coming from the gastrointestinal tract. A certain amount of liver damage can result from an excess of food, alcohol, drugs, toxicants, and other harmful substances impairing proper hepatic function, which may indicate irregularities in the processing and secretory functions of hepatocytes. Evidence of damaged hepatocellular structures and abnormal liver function brought on by elevated activity of serum biochemical markers are indicators of hepatic injury. Because oxidative stress can primarily oxidize components of the hepatocellular structure, like DNA, proteins, and lipids, ROS may play a major role in the development and aggravation of liver dysfunction. Pathological apoptosis releases toxic cytokines and creates a powerful immune response that kills hepatocytes in excess.

High-fat, high-cholesterol, high-triglyceride, and high-fructose diets markedly increased serum AST and ALT levels, which were markedly reduced by extracts of hawthorn fruit, also known as Crataegus pinnatifida (C. pinnatifida) under its latin’s name. By inhibiting oxidative injury and apoptosis, hawthorn extracts protect against liver damage caused by high-fat, cholesterol, triglyceride, and fructose diets, alcohol therapy, LPS, CCl4, cadmium, and partial

hepatectomy in rodents and HepG2 cells. Because abnormal hepatocellular integrity causes serum transaminase (AST and ALT) to leak into peripheral blood, these levels are often elevated in liver injury. Therefore, maintaining both serum markers within normal ranges can be seen as protecting the liver and maintaining liver function.

Following alcohol exposure, C. pinnatifida is involved in preventing liver damage. Alcohol poisoning resulted in aberrant alcohol-metabolizing enzyme activity, biochemical marker levels, increased DNA damage in liver cells, and histological findings in HepG2 cells and Sprague Dawley rats. Following the administration of an ethanol extract containing C. pinnatifida to these rats, there was an increase in ALDH activity in the hepatic tissues, along with a decrease in serum levels of AST, ALT, and GGT, as well as an improvement in cell necrosis and sinusoidal distension.

What gives C. pinnatafia its liver reversing qualities is its chemical composition of the numerous flavonoids, triterpenoids, monoterpenoids, lignans, and organic acids that can be found in hawthorn. Its leaves, flowers, and berries have yielded the identification of more than 150 chemical compounds to date. Ursolic acid is utilized for the fruit identification test of C. pinnatifida, as per the Korean and People’s Republic of China pharmacopoeias, which recognize C. pinnatifida as the representative species of hawthorn. The People’s Republic of China’s pharmacopoeia states that the fruits and leaves of C. pinnatifida should have a content of at least 5.0% citric acid, 7.0% flavonoids, and 0.050% hyperoside. From the leaves and flowers of C. pinnatifida, flavones have been isolated and identified and their aglycone is luteolin.

One tetrahydroxy flavone that is glycosylated is luteolin (C15H10O6, 3′,4′,5,7-Tetrahydroxyflavone).

Its anti-inflammatory and antioxidant properties as flavonoids were undoubtedly enhanced by the ortho dihydroxy group on the B ring and the presence of OH at the C-5 position on the A ring. The catechol ring in the chemical structure of luteolin is replaced by 2,2′-azobis(2-amidinopropane) dihydrochloride modification, which allows it to avoid the methylation reaction catalyzed by catechol-O-methyltransferases (COMT), maintain its anti-inflammatory and other activities when administered, and continue to function in its original form. It is crucial to choose flavonoid screening compounds with fewer phenolic hydroxyl groups. While luteolin’s phenolic hydroxyl groups are small in comparison to some well-known phenolic compounds, a high concentration of phenolic groups may decrease oral absorption. The density was 1.654 g/cm3, and the molecular weight was 286.24.

Lipopolysaccharide (LPS) is an endotoxin found in the outer membrane of gram-negative bacteria. It interacts with TLR4 to trigger a pro-inflammatory signaling cascade, activating the classical and lectin pathways. Lipopolysaccharide (LPS) has been linked to both acute and chronic liver injury. Numerous intricate processes, including oxidative stress, autophagy, apoptosis, and inflammation, are part of the molecular mechanism of pathogenesis. Of these, the majority of acute liver injuries share an inflammatory pathogenesis. One thioredoxin-binding protein that is important in oxidative stress is called thioredoxin interacting protein (TXNIP). Under oxidative stress, it directly activates the NOD-like receptor thermal protein domain associated with protein 3 (NLRP3) inflammasome; however, the TXNIP-NLRP3 axis has not received much research attention. Luteolin prevented the activation of the NLRP3 inflammasome by inhibiting TXNIP, caspase-1, IL-1β, and IL-18. This lessened liver damage. Put differently, it prevented mice from suffering acute liver damage caused by lipopolysaccharide by blocking the TXNIP-NLRP3 axis. Furthermore, luteolin reduced hepatocyte damage caused by lipopolysaccharide by preventing oxidative stress and controlling the levels of glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). High mobility histone box 1 protein (HMGB1), which is extensively distributed and regarded as an alarm factor, is a significant inflammatory factor in sepsis. By inducing the recruitment and activation of macrophages and interacting with other endogenous and exogenous molecules like LPS, it promotes the migration of neutrophils. Luteolin may also control the release of HMGB1 via the P2X7 receptor-glycation end products-Toll-like receptor 4 (P2X7R-RAGE-TLR4) axis. This would control the NLRP3 inflammasome and, in turn, lessen inflammatory infiltration and LPS-induced septic acute liver injury. Furthermore, luteolin pretreatment may not only inhibit this process to lessen liver injury but also control autophagy and apoptosis by means of the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor α (ERK/PPARα) pathway. Hepatic ischemia-reperfusion injury also activates Kupffer cells, which in turn produces a variety of inflammatory cytokines.

Since luteolin has four hydroxyl groups, it can produce a wide variety of derivatives. These locations can be connected to various kinds of functional groups or sugar molecules to create structurally related molecules. The more popular ones are methyl derivatives and glycosides with the ends -C and -O. Lutein-7-O-glucoside has been reported to significantly reduce GalN/LPS induced liver toxicity in the model of acute liver injury in mice induced by galactosamine (GalN) and LPS. This is achieved by reducing the activity of phase II enzymes and regulating inflammatory mediators like Nrf2. 4’,5,7-Trihydroxyflavone,

Its chemical structure does not contain a catechol ring, which could evade COMT-catalyzed methylation and increase the anti-inflammatory effect. Furthermore, two other significant luteolin derivatives are luteolin-8-C-glucoside and luteolin-6-C-glucoside. Lutein-8-C-glucoside specifically reduced the level of pro-oxidants and increased the activity of antioxidant enzymes in the liver and serum, which may be connected to the activation of Nrf2/ARE by the PI3K/AKT and p38/MAPK signaling pathways. The luteolin-6-C-glucoside compound has been shown to be a DNA damaging agent. It has been shown to cause hepatoblastoma (HB) cells to undergo apoptosis by causing DNA double strand breaks and obstructing the initial process of homologous recombination repair. Additionally, it has been shown to significantly suppress HB cell proliferation both in vitro and in vivo. These effects are closely associated with the reduction of ATM activation and the inhibition of the binding of phosphorylated ATM (PATM) and MRE 11-RAD 50-NBS 1 (MRN) complex.

Overall, extracts from hawthorn are beneficial against cancer, fibrosis, inflammation, fat deposition, and hepatic toxicity.The chemical lutein in C. pinnatifida aka hawthorn fruit reverses the negative effects of strain to the liver from alcohol abuse do to its ability to decrease oxidative stress.

Work Cited:

• Kim, Eujin, et al. “Potential Roles and Key Mechanisms of Hawthorn Extract againstVarious Liver Diseases.” Nutrients, U.S. National Library of Medicine, 18 Feb. 2022,www.ncbi.nlm.nih.gov/pmc/articles/PMC8879000/.
• Wu, Jiaqi, et al. “Crataegus Pinnatifida: Chemical Constituents, Pharmacology, andPotential Applications.” Molecules (Basel, Switzerland), U.S. National Library ofMedicine, 30 Jan. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC6271784/.
• Yao, Chenhao, et al. “Luteolin as a Potential Hepatoprotective Drug: MolecularMechanisms and Treatment Strategies.” Biomedicine & Pharmacotherapy, vol. 167, Nov.2023, p. 115464. https://doi.org/10.1016/j.biopha.2023.115464. –