**6.1 Flavonoids**

Flavonoids are herbal medicines that are given orally. This drug was originally indicated as a blood vessel strengthening agent (venotonic) and an anti-edema agent in the treatment of varicose veins in the legs. These flavonoids have been studied in varicose veins. They have the ability to increase vascular tone, decrease venous capacity, decrease capillary permeability, increase lymphatic drainage, and have antiinflammatory effects. Although the mechanism of healing in hemorrhoids is not clear, this drug has been widely used in Europe and Asia. The micronized purified flavonoid fraction (MPFF) consisting of 90% diosmin and 10% hesperidin is the most commonly used flavonoid in clinical practice. This fine shape (less than 2 microns in size), allows absorption to be easier so that it works faster [13].

A recent meta-analysis showed that MPFF treatment provided significant benefits for bleeding (odds ratio [OR] 0.082, p < 0.001), discharge/leakage (OR 0.12, p < 0.001), and overall improvement according to patients (OR 5.25, p < 0.001) and investigators (OR 5.51, p < 0.001). MPFF also reduces pain (OR 0.11, P = 0.06) [14]. The recommended dose in the acute phase is 3x1 gr in the first 3–4 days and then decreases to 2x1 gr. The medication can be stopped gradually, according to the patient's response. Long-term use of this medication is reported to be safe. The medication is also reported to be safe to be used in pregnant women [13].

Purple leaf (Grapthopylum pictum extract/GPE), which also contains flavonoids, has been shown to be useful in improving the complaints of hemorrhoids in developing countries. In a study for patients with hemorrhoids, with a pre and post-test-only group design, it was reported that GPE reduces the signs and symptoms [15]. In animal studies, inducing anal Wistar rats with croton oil, showed that GPE, reduces inflammatory markers [16], accelerates ulcer healing [17], and reduces edema [18]. Currently, in Indonesia, GPE can be considered a standardized herb. To be recognized as a phytopharmaca, it needs to be continued with better clinical trials.
