Current options for conservative treatment of hemorrhoidal disease: the role of natural bioactive compounds and indications for surgical intervention

Why Does Hemorrhoidal Disease Remain a Relevant Medical Problem?

Hemorrhoidal disease is among the most common disorders of the anorectal region and is one of the principal reasons patients seek specialist care. Although the disease has been known to medicine for many centuries, current understanding of its pathogenesis has changed substantially. Whereas hemorrhoids were previously viewed primarily as a consequence of varicose dilation of the hemorrhoidal veins, their development is now associated with a complex of vascular, inflammatory, and degenerative changes accompanied by impaired microcirculation, damage to the supporting ligamentous apparatus, and chronic inflammation.

According to epidemiological studies, clinical manifestations of hemorrhoids occur at various periods of life in almost 40% of the adult population. The highest prevalence is observed among patients older than 45 years, pregnant women, and people with chronic constipation, obesity, and a sedentary lifestyle. However, the actual prevalence of the disease is probably considerably higher than official statistics suggest because many patients self-medicate for long periods and seek medical attention only after complications develop.

Hemorrhoids are a common disease. Treatment ranges from conservative approaches to surgical interventions.

Modern hemorrhoid therapy is aimed not only at eliminating symptoms but also at influencing the principal pathogenetic mechanisms of the disease. This explains the growing interest in agents capable of simultaneously reducing inflammation, improving venous outflow, restoring microcirculation, and stimulating tissue repair.

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What Determines the Choice of Treatment Method?

Hemorrhoidal disease is classified into internal, external, and mixed forms. The Goligher classification, based on the degree of prolapse of internal hemorrhoids, is the most widely used in clinical practice. Four stages of the disease are distinguished. The disease stage determines the treatment strategy.

During the early stages, in the absence of pronounced prolapse, preference is given to conservative treatment, including lifestyle modification, elimination of risk factors, normalization of bowel movements, and pharmacological therapy. In stage III–IV disease, accompanied by persistent hemorrhoidal prolapse, severe pain, or recurrent bleeding, the role of surgical treatment increases substantially.

Thus, the modern approach does not involve opposing therapeutic and surgical methods but instead applying their rational combination according to the clinical presentation of the disease.

Why Does Conservative Therapy Remain the Basis of Early-Stage Treatment?

The principal objectives of pharmacological therapy are to reduce the inflammatory response, eliminate venous stasis, decrease vascular-wall permeability, relieve pain, and prevent disease progression.

Standard therapy includes increasing dietary fiber intake, correcting constipation, and using topical preparations and systemic phlebotropic agents. This approach reduces the severity of the main symptoms and substantially improves patients’ quality of life.

The basis of conservative therapy has traditionally consisted of phlebotonics and angioprotectors:

• Diosmin: rapidly reduces capillary permeability, stops bleeding, and decreases edema and pain during acute attacks.
• Troxerutin: frequently used in combinations to achieve a synergistic effect.
• Hydroxyethylrutosides: stabilize the vascular wall, reduce inflammation, and improve lymphatic outflow.
• Calcium dobesilate: reduces blood viscosity, improves tissue drainage, and rapidly blocks bleeding and inflammatory processes.

However, most commonly used medicines predominantly affect individual clinical manifestations of the disease. For example, local anesthetics reduce pain, vasoconstrictors limit bleeding, and venotonics improve venous outflow. Meanwhile, hemorrhoidal pathogenesis is considerably more complex and includes an interconnected cascade of processes: chronic inflammation, oxidative stress, impaired microcirculation, endothelial damage, connective-tissue degradation, and delayed regeneration.

For this reason, particular attention in recent years has been given to natural bioactive compounds capable of simultaneously influencing several pathogenetic mechanisms.

Why Are Natural Bioactive Compounds Generating Such Interest?

Plant polyphenols, flavonoids, terpenoids, phenolic acids, and other natural compounds have a broad spectrum of biological activity. Unlike most symptomatic medicines, they can simultaneously regulate the inflammatory response, reduce vascular-wall damage, improve microcirculation, limit oxidative stress, and stimulate tissue restoration.

This multitarget action is considered the principal advantage of natural compounds and explains the growing interest in studying them.

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Effects on the Inflammatory Response

Chronic inflammation is one of the key factors contributing to the progression of hemorrhoidal disease. Damage to the vascular wall is accompanied by activation of macrophages, neutrophils, and endothelial cells, which begin actively synthesizing proinflammatory cytokines, including TNF-α (tumor necrosis factor-alpha), IL-1β, and IL-6 (interleukin-6).

These mediators sustain the inflammatory process, increase vascular permeability, promote edema, and intensify pain.

Many natural polyphenols can inhibit the transcription factor NF-κB (nuclear factor kappa B), a central regulator of the inflammatory response. Its suppression is accompanied by reduced expression of cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), metalloproteinases, and proinflammatory cytokines. At the same time, the activity of the MAPK (mitogen-activated protein kinase) and AP-1 (activator protein-1) signaling pathways decreases, further limiting the inflammatory response.

The most extensively studied inhibitors of these signaling cascades are potent plant polyphenol antioxidants:

• Epigallocatechin-3-gallate (EGCG): the principal polyphenol in green tea.
• Curcumin: the main active ingredient of turmeric root.
• Resveratrol (a stilbenoid): found in grapes and Japanese knotweed.
• Quercetin (a flavonol): found in onions, apples, and buckwheat.
• Apigenin (a flavone): found in parsley and chamomile.

Through their complex effects on different components of inflammation, these compounds may not only reduce symptom severity but also potentially slow disease progression.

Protection of the Vascular Wall and Improvement of Microcirculation

Damage to the vascular endothelium is accompanied by impaired venous tone, increased capillary permeability, and the formation of local venous stasis. These changes underlie enlargement of hemorrhoids and the development of bleeding.

Flavonoids, particularly diosmin and hesperidin, increase venous-wall tone, reduce venous distensibility, decrease capillary permeability, and improve lymphatic drainage. The pronounced antioxidant effect of these compounds is also important. By binding reactive oxygen species, they protect endothelial cells from oxidative damage, restore nitric oxide bioavailability, and contribute to normalization of microcirculation.

Antioxidant Activity as a Component of Pathogenetic Therapy

One comparatively new area of research concerns the role of oxidative stress in hemorrhoidal disease. Chronic inflammation is accompanied by excessive generation of reactive oxygen species, damage to cell membranes, activation of lipid peroxidation, and endothelial dysfunction.

Polyphenols, including quercetin, resveratrol, green-tea catechins, and phenolic acids, can considerably reduce free-radical formation and increase the activity of superoxide dismutase, catalase, and glutathione peroxidase. This helps reduce oxidative tissue damage and creates favorable conditions for restoration of the vascular wall.

Hemostatic Effects

Bleeding is one of the most frequent symptoms of hemorrhoidal disease. Some natural compounds can enhance local hemostasis through moderate vasoconstrictive effects, increased vascular-wall resistance, and improved interaction between platelets and the damaged endothelium.

At the same time, reducing the severity of inflammation decreases secondary capillary damage, which also helps reduce bleeding.

Antimicrobial Activity

Current studies indicate that disruption of the local microbial balance can sustain chronic inflammation in the perianal region. Many plant polyphenols have pronounced antibacterial activity against Escherichia coli, Staphylococcus aureus, and other opportunistic microorganisms. In addition to a direct antimicrobial effect, they can prevent the formation of bacterial biofilms and reduce the inflammatory response induced by microbial toxins.

Stimulation of Regenerative Processes

Healing of the damaged mucosa is one of the most important stages in hemorrhoid treatment. Studies indicate that several natural compounds activate the expression of the growth factors TGF-β (Transforming Growth Factor β), PDGF (Platelet-Derived Growth Factor), and FGF (Fibroblast Growth Factor) and stimulate fibroblast proliferation, collagen synthesis, and extracellular-matrix formation.

Consequently, epithelialization of the damaged mucosa accelerates, connective-tissue strength increases, and the likelihood of repeated vascular-wall damage decreases. Particularly pronounced regenerative potential has been described for curcumin, glycyrrhizin (an active triterpenoid saponin from licorice root), aloe vera, resveratrol, and several plant extracts.

When Does Surgical Treatment Become Preferable?

Despite substantial progress in conservative therapy, surgical methods remain the most effective means of achieving a durable clinical result in patients with pronounced hemorrhoidal prolapse and advanced stages of the disease. Current meta-analyses indicate that surgical treatment provides faster symptom resolution and is associated with a lower recurrence rate than exclusively pharmacological therapy, although it involves a longer recovery period and a higher risk of postoperative discomfort.

From Symptomatic Treatment to Pathogenetic Therapy

Current understanding indicates that hemorrhoidal disease is a multifactorial disorder based on a combination of vascular abnormalities, chronic inflammation, oxidative stress, and connective-tissue degeneration. Effective therapy should therefore be directed not only at eliminating symptoms but also at correcting the principal pathogenetic mechanisms.

Conservative treatment remains the method of choice during the early stages of the disease, whereas surgery retains a leading role in pronounced hemorrhoidal prolapse and complicated disease. At the same time, recent research findings indicate considerable potential for natural bioactive compounds as components of combination therapy. Their ability to simultaneously influence inflammation, oxidative stress, microcirculation, vascular permeability, and regenerative processes makes this one of the most promising areas in modern coloproctology. Nevertheless, a definitive assessment of the effectiveness of natural compounds requires further large randomized clinical trials to establish their place in clinical guidelines and routine practice.

References

1. «Comparison of efficacy and safety between surgical and conservative treatments for hemorrhoids: a meta-analysis». Longfang Quan at al, BMC Gastroenterology, 2025
2. «Natural Products with Potential Effects on Hemorrhoids: A Review» Yicheng Liang at al, «Molecules», 2024