Preclinical Insights into the Therapeutic Potential of Hawthorn in Hypertension Management: A Review

Abstract

Hypertension, often referred to as the ‘silent killer,’ is a leading contributor to cardiovascular diseases worldwide, with its prevalence increasing at an alarming rate. As cases of hypertension continue to rise globally, there is a growing interest in exploring natural remedies as either alternatives or complements for conventional antihypertensive drugs. Among the natural solutions, Crataegus species, commonly known as Hawthorn belonging to the Rosaceae family have attracted considerable attention due to their rich phytochemical composition, which may provide potential therapeutic benefits in managing hypertension. This review highlights the preclinical evidence from in vivo and in vitro studies on Hawthorn extracts, focusing on their vasodilatory, antioxidant, and anti-inflammatory properties. These preparations have demonstrated the ability to regulate nitric oxide production, alleviate oxidative stress, and reduce vascular inflammation key processes in managing blood pressure. Additionally, animal studies have assessed the relative effectiveness of several Crataegus species and their prospective combination with conventional antihypertensive medications. The studies emphasize Hawthorn's role as a promising natural alternative or supplement for addressing hypertension and its associated cardiovascular risks.

Keywords

Antihypertensive effect, Crataegus species, Hawthorn, Herbal medicine, Hypertension, Preclinical studies

Introduction

The cardiovascular advantages of hawthorn, a powerful herbal treatment, are ascribed to bioactive substances such as phenolic acids, proanthocyanidins, and flavonoids. These improve coronary circulation, myocardial oxygen utilization, and heart function in general, all of which contribute to heart health. Hawthorn has broader medicinal potential, including lowering inflammation, preventing atherosclerosis, and reducing plaque accumulation, according to recent study. Hawthorn may also protect against infection, control blood sugar and cholesterol, and enhance liver function. Its potential as an antidepressant and neuroprotective benefits against Alzheimer’s disease increase its value. Although encouraging, additional clinical research is required to thoroughly examine and maximize its medicinal uses.

1. Anti-atherosclerosis:

Atherosclerosis develops as a result of activated vascular inflammation, which can also lead to endothelial activation and the production of foam cells. The impact of Hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis in mice was examined. The findings showed that in apo-lipoprotein E knock-out mice fed a high-fat western diet, trimethylamine-N-oxide (TMAO) increased atherogenesis, worsened inflammation, and aggravated oxidative stress. In mice fed a diet containing TMAO HFE prevented the development of atherosclerotic plaque. Mice given a high-fat TMAO-containing diet showed elevated plasma levels of TNF-α, IL-1β, and MCP-1, while mice given an HFE supplement showed a dose-dependent decrease in plasma levels of TNF-α and MCP-1. TMAO elevated hepatic mRNA expression of the three proinflammatory cytokines. Dietary TMAO raised MDA plasma levels, decreased plasma SOD and GSH-Px activity, and decreased plasma T-AOC. There was a decrease in the hepatic activity of SOD and CAT³³.

2. Anti-hepatic fibrosis:

The effects of Crataegus oxyacantha were studied in rats with carbon tetrachloride induced hepatic fibrosis. They discovered that CCl4 exposure increased oxidative stress, as seen by elevated levels of malondialdehyde (MDA) and protein carbonyls, as well as decreased activity of superoxide dismutase (SOD). This oxidative stress was accompanied with necrosis, as seen by elevated serum levels of liver enzymes. The study found elevated levels of inflammation markers in the liver, which led to hepatotoxicity and activation of hepatic stellate cells. HAW (Crataegus oxyacantha) therapy reduced oxidative stress, as shown by decreased MDA and protein carbonyl levels, and restored SOD function in the liver. It also reduced the release of ROS and fibrogenic mediators while decreasing inflammatory cell recruitment. HAW suppressed α-SMA-producing cells, slowing the advancement of hepatic fibrosis and reducing collagen changes caused by CCl4³⁴.

3. Anti-diabetic:

The hypoglycaemic and hypolipidemic effects of an ethanolic extract of C. aronia and C. aronia-phytosome were examined in streptozotocin (STZ)-induced diabetic rats. The study found that C. aronia leaves extract and C. aronia-p effectively lowered blood glucose levels in diabetic rats. The reduction in blood glucose levels was due to increased insulin secretion and decreased oxidative stress in pancreatic beta cells. Inhibition of carbohydrate-hydrolyzing enzymes such as α-amylase and glucosidase may diminish glucose absorption in the intestine, contributing to the observed impact. An increased risk of cardiovascular disease, type 2 diabetes, and certain cancers, such as colorectal, pancreatic, and breast cancer, is linked to insulin resistance and obesity. When compared to untreated rats, diabetic rat’s body weight has been demonstrated to increase with C. aronia-p and its ethanolic extract. Enhanced insulin sensitivity and decreased blood sugar levels have a close connection to weight loss. TG, TC, and LDL-C levels were decreased in a diabetic rat model by C. aronia-p and an ethanolic extract of C. aronia³⁵.

4. Anti-bacterial:

The lowest inhibitory concentration (MIC) values in the investigation showed that the separated flavonoids had higher in vitro antibacterial activity than the crude extract. Additionally, using DPPH tests, the dried extract showed noteworthy antioxidant qualities. Using susceptibility and MIC tests, the antibacterial activity of the Hawthorn fruit extract was assessed against Staphylococcus aureus and Escherichia coli. These two dangerous bacterial strains were used to test the bactericidal qualities of Crataegus oxyacantha’s flavonoid and crude extracts. Three Gram-negative and two Gram-positive bacteria were tested for the study. Notably, Gram-positive bacteria can be distinguished from Gram-negative bacteria by retaining the crystal violet stain employed in the Gram staining process. The extracts showed antibacterial activity against every germ that was tested³⁶.

5. Anti-Alzheimer:

The effects of Crataegus pinnatifida (CPE) fruit on symptoms similar to Alzheimer's disease were examined using a mouse model of Aβ-induced memory impairment and assessed using the passive avoidance test. Using the Thioflavin T (ThT) assay, the study examined how CPE affected Aβ-induced glial activation and Aβ fibril production. Measurement of Aβ-induced neuronal cell death was used to assess CPE's capacity to prevent Aβ toxicity. In the DAPI staining assays, higher CPE dosages significantly decreased Aβ cytotoxicity. Memory impairments brought on by Aβ fibrils were successfully remedied by CPE. In the hippocampal dentate gyrus region, CPE inhibited the rise in astrocytes and microglia brought on by Aβ. CPE increased its protective effects by dissolving pre-existing fibrils in addition to preventing Aβ aggregation. Glial cell counts in the hippocampus rose and memory impairments were caused by intracerebroventricular (i.c.v.) injection of Aβ fibrils. CPE was able to lessen these effects³⁷.

6. Anti-depressant:

The effects of C. aronia on neurotransmitter levels and depressive-like symptoms in rats exposed to chronic unexpected mild stress (CUMS) were examined. The rats' serotonin (5-HT) levels dropped after stress exposure, whereas their dopamine (DA) and norepinephrine (NE) levels rose. Elevated urine serotonin levels and decreased NE and DA levels were indicative of a considerable reversal of the depressive-like symptoms following treatment with C. aronia. These neuromodulatory effects were similar to those of the widely prescribed antidepressant fluoxetine. By modifying the central monoamines, such as 5-HT, NE, and DA, the active ingredients of C. aronia more especially, anthocyanins and procyanidins contributed to its antidepressant-like effects. The administration of aqueous extract of C. aronia (AECA) successfully corrected the altered neurotransmitter levels in CUMS-stressed rats, bringing them into line with those of rats treated with fluoxetine. Additionally, C. aronia's high polyphenolic content may help reduce oxidative stress brought on by CUMS, which would increase its antidepressant effect³⁸.

7. Anti-genotoxicity:

Benzo(a)pyrene (BaP), a strong carcinogen and mutagen that is frequently produced by environmental pollution and food processing techniques like roasting and frying, causes serious health hazards. Hawthorn extract (HE) contains a lot of phenolic chemicals, such as epicatechin (2.99 mg/g dry weight), procyanidin B2 (3.58 mg/g), and chlorogenic acid (2.78 mg/g), which may help explain its anti-genotoxic qualities. The International Agency for Research on Cancer (IARC) has designated BaP as a carcinogenic substance and acknowledges it as a highly hazardous member of the polycyclic aromatic hydrocarbons (PAHs) class. The study assessed HE's ability to prevent DNA damage and related tissue damage caused by BaP. Hepatic vacuolization, inflammatory lung cell infiltration, and splenic cord and sinusoid damage brought on by BaP were all significantly reduced in mice given HE. To further examine the antioxidative effects of HE against BaP, the amounts of reactive oxygen species (ROS) in the bone marrow cells of mice treated with BaP were measured using flow cytometry. BaP-induced G1 cell cycle arrest was significantly lessened by HE treatment, indicating a protective effect associated with a decrease in double-strand breaks (DSBs)³⁹.

8. Anti-platelet:

The extract of C. aronia syn. Azarolus (L) was tested for its anti-platelet properties. In addition to being necessary for hemostasis, activated platelets play a role in the pathological development of certain arterial illnesses, including acute coronary syndromes and strokes, which are caused by plaque breakdown and the ensuing formation of platelet-thrombus. Platelets aggregate in response to endogenous agonists such as collagen, thrombin, platelet activating factor, adenosine diphosphate (ADP), and arachidonic acid (AA). The aqueous C. aronia syn. Azarolus (L) extract significantly altered the bleeding and closure times, showing a significant suppression of platelet function based on the PFA-100 and thromboxane B2 levels. Doses ranging from 100 to 500 mg/kg of C. aronia produced 1,000 mg/kg of thromboxane B2, but the higher dose (2,000 mg/kg) had the opposite impact on these parameters. Aspirin was administered to the active control group. Oral treatment of aqueous whole-plant C. extract decreased collagen, ADP, and collagen/epinephrine-induced platelet aggregation⁴⁰.

Nutritional Value and Traditional Uses:

1. Culinary uses:

The food sector is using hawthorn more and more because of its numerous uses and health advantages. It is a common component of functional foods due to its high polyphenol content and antioxidant qualities, particularly in China, where there is a rising market for goods manufactured from hawthorn. There is no need to clean or fumigate fresh hawthorn fruit before eating it, and a variety of superior goods have been created to satisfy consumer demands. Developments in membrane processes, homogenizers, and enzyme technologies have increased the uses of hawthorn. Typical hawthorn items include canned hawthorn, hawthorn chips, sweet gourds, hawthorn preserves, baked goods, snacks, wines, and jams⁴¹.

2. Hawthorn Jam:

Jam is becoming more and more popular among consumers as the ideal accompaniment to breads and other pastries. The two main categories of hawthorn jams currently available on the market are “regular hawthorn jam” and “compound jams” that contain hawthorn taste, like “hawthorn leaf flavonoid jam” and “hawthorn passion fruit jam”. Ingredients like 1.15% hawthorn leaf flavonoids, 45% white sugar, 0.30% pectin, 0.20% xylitol, and 0.16% citric acid are needed to make flavourful hawthorn leaf flavonoid jam. In addition to satisfying the demand for a nutritious and safe jam, the blend of hawthorn jam also improves the use of hawthorn berries⁴¹.

3. Hawthorn in Bakery Products:

When making hawthorn "bakery goods," it is essential to use effective methods to maintain the active elements and enhance the hawthorn's absorbing and dissolving properties. to improve its distinct flavor and health advantages. Hawthorn bread is made using ultra-fine grinding technology, 3% hawthorn powder, 0.6% salt, 18% sugar, and 0.5% bread amendment. This raw material can be consumed by those with type 2 diabetes. When added to whole wheat flour bread, it also has an antihyperglycemic effect and supports healthy circulatory and gastrointestinal function⁴¹.

4. Hawthorn based Fruit Wines and Beverages:

Fruit-based wines and beverages made from hawthorn are becoming more and more well-liked because of the fruit's high vitamin, mineral, and bioactive chemical content. Varieties produced from the star-spotted hawthorn shrub in North America offer better flavour, fragrance, clarity, and overall quality, while hawthorn, with its high polyphenol and antioxidant content, improves the nutritional profile of these wines. By reducing pH and releasing methyl groups, treatments like pectinase speed up the clarifying process and improve the final product. Hawthorn is also used to enhance flavour and give extra health benefits in confections like fondant. as the market for goods made from hawthorn grows. Further potential for the hawthorn industry is provided by this biomass, which is high in xylan (28%) and may be used to create value-added products like oligosaccharides and xylose (XOS)⁴¹.

Conclusion and Future Remarks:

A promising natural treatment with notable antihypertensive benefits, hawthorn (Crataegus spp.) is a good choice for controlling high blood pressure. According to preclinical studies Hawthorn has shown promise in improving cardiovascular function, blood flow, lowering vascular resistance, and promoting heart health through its diverse range of bioactive components, especially flavonoids, proanthocyanidins, and phenolic acids. By reducing inflammation and oxidative stress in the vascular system, its strong anti-inflammatory and antioxidant qualities also help to decrease blood pressure. Studies conducted both in vitro and in vivo offer strong proof of hawthorn's ability to control blood pressure, highlighting its potential as a secure and efficient supplement to traditional treatments for hypertension. Further demonstrating hawthorn's therapeutic potential in treating not only hypertension but also associated cardiovascular disorders like atherosclerosis are its methods of action, which include vasodilation, nitric oxide generation, and platelet inhibition. Hawthorn's use as an alternative or complementary treatment for hypertension could have a big influence on public health as the disease's prevalence rises worldwide. Hawthorn extract’s clinical effectiveness and safety in human populations must be confirmed by additional study, including well planned clinical studies. The standardization of hawthorn preparations, the best dosage, and long-term safety should be the main topics of future research in order to fully utilize their potential in the treatment of hypertension and associated cardiovascular disorders. Overall, Hawthorn is a beneficial supplement to both herbal medicine and contemporary healthcare, providing a safe, easy, and effective way to enhance cardiovascular health.

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