The stem bark decoction of Myrianthus arboreus P. Beauv. (Cecropiaceae) shows anti-uterine leiomyoma effects in Wistar rat

Abstract

Abstract: Over the past 30 years, the number of new cases of uterine leiomyomas (UL) in women of reproductive age has increased by 67.14% worldwide. The limitations of the current therapeutic options have led to the search for alternatives. Myrianthus arboreus P. Beauv., used for infertility and tumors, has never been tested for UL. In the present study, the decoction of its stem bark was evaluated in a model of UL induced in female Wistar rats. Animals were treated once daily by gavage for 30 days. Normal control and model groups received distilled water, positive groups received mifepristone (5.2 mg/kg) and the remaining three groups were treated with 50, 100, and 200 mg/kg M. arboreus extract, respectively. Compared to the model group, the extract at 50 and 100 mg/kg reduced the E2B- and progesterone-induced uterine horn asymmetry and thickening, and the relative uterine weight and diameter; myometrial thickness; and collagen density (at 100 and 200 mg/kg). Regarding cytokines, the extract decreased the uterine levels of TGF-β1 and VEGF (at 100 and 200 mg/kg) and TNF-α (at all doses tested). It also decreased the serum levels of estradiol (at 100 and 200 mg/kg). Despite positive trend in reducing oxidative damage (decreased MDA at 50 mg/kg, increased catalase activity at all tested doses, and increased GSH at 100 mg/kg), the level of oxidative stress is still elevated. By attenuating key cellular events involved in the growth and development of UL, such as inflammation, fibrosis and angiogenesis, Myrianthus arboreus may be a promising option for UL treatment and management.

Lay summary: Uterine fibroids are non-cancerous tumors that originate from the smooth muscular wall of the uterus. They may cause severe symptoms, such as chronic pelvic pain, heavy menstrual bleeding, painful intercourse, frequent urination, back pain and obstetric complications (embryo implantation failure, fetal growth restriction, miscarriages, preterm delivery, and fertility impairment). The exact cause is not known, but hormonal changes may play an important role. Treatment options depend on the symptoms and desire to preserve the uterus, and may include medication, minimally invasive procedures and surgery. Their associated risks and limitations fuel searching for conservative alternatives. This study investigates the anti-uterine fibroid potential of the giant yellow mulberry (Myrianthus arboreus P. Beauv.) in rat. Consuming boiled M. arboreus stem bark in water reduced uterine wall thickness, inflammation, and collagen deposition, and increased the ability of the uterus to fight cell damage. Thus, this extract may prevent or shrink uterine fibroids by reducing uterine swelling, fibrosis and excessive cell growth.

Keywords: Myrianthus arboreus P. Beauv.; Wistar rat; anti-tumoral properties; stem bark; uterine leiomyomas.

Figure 1

Body weight evolution during the UL induction and treatment periods. NG₁: normal group receiving corn oil (50 μL/kg BW/day i.m.); MG₁: model group receiving 17β-estradiol benzoate and progesterone. NG₂ (normal group) and MG₂ (model group) received distilled water; mifepristone: model rats treated with mifepristone (5.2 mg/kg/day). MA50, MA100 and MA200: model rats treated with the decoction of M. arboreus at doses of 50, 100 and 200 mg/kg BW/day, respectively. **P < 0.01 and ***P < 0.001 vs NG₁.

Figure 2

Morphological and histological changes (hematoxylin–eosin, ×200 magnification, scale bar: 100 µm) in the uterus after the UL induction and treatment periods. Arrows: nodules/swelling; NG₁: normal group receiving corn oil (50 μL/kg BW/day i.m.); MG₁: model group receiving 17β-estradiol benzoate and progesterone. NG₂ (normal group) and MG₂ (model group) received distilled water; mifepristone: model rats treated with mifepristone (5.2 mg/kg/day). MA50, MA100 and MA200: model rats treated with the decoction of M. arboreus at doses of 50, 100 and 200 mg/kg BW/day, respectively. *P < 0.05, **P < 0.01, ****P < 0.0001 vs NG; ^#P < 0.05, ^##P < 0.01, ^###P < 0.001 vs MG.

Figure 3

Uterine levels of pro-inflammatory, angiogenic and oxidative stress biomarkers after the UL induction and treatment periods. NG₁: normal group receiving corn oil (50 μL/kg BW/day i.m.); MG₁: model group receiving 17β-estradiol benzoate and progesterone. NG₂ (normal group) and MG₂ (model group) received distilled water; mifepristone: model rats treated with mifepristone (5.2 mg/kg/day). MA50, MA100 and MA200: model rats treated with the decoction M. arboreus at doses of 50, 100 and 200 mg/kg BW/day, respectively. *P < 0.05, **P < 0.01, ****P < 0.0001 vs NG; ^#P < 0.05, ^##P < 0.01, ^###P < 0.001, ^####P < 0.0001 vs MG.

Figure 4

Serum estradiol and progesterone levels after the UL induction and treatment periods. NG₁: normal group receiving corn oil (50 μL/kg BW/day i.m.); MG₁: model group receiving 17β-estradiol benzoate and progesterone. NG₂ (normal group) and MG₂ (model group) received distilled water; mifepristone: model rats treated with mifepristone (5.2 mg/kg/day). MA50, MA100 and MA200: model rats treated with the decoction M. arboreus at doses of 50, 100 and 200 mg/kg BW/day, respectively. *P < 0.05 and **P < 0.01 vs NG; ^#P < 0.05 vs MG.