Acute and subacute toxicological evaluation of the ethanol leaf extract of Morus mesozygia stapf. (Moraceae) in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the Morus mesozygia tree leaf has been used to manage maladies such as peptic ulcer, hyperglycemia, dermatitis, rheumatism, stomach-ache, arthritis, cough, malignancies, and malaria in parts of Africa. AIM OF THE STUDY: The study aimed to evaluate the potential of ethanol leaf extract of Morus mesozygia (EEMm) to induce toxicity by employing both acute and sub-acute oral toxicity experimental models. MATERIAL AND METHODS: The extract's cytotoxicity was studied using brine shrimps (Artemia salina) lethality assay (BSLA), while in the acute toxicity test, male and female mice were administered a single oral dose of EEMm (2000 mg/kg). Male and female Wistar rats received repeated doses of 100 or 500 mg/kg EEMm orally for 28 days in the sub-acute toxicity experiment. The phytochemical analysis of EEMm was done using the HPLC. RESULTS: The BSLA revealed a moderate cytotoxic potential of the extract, with an LC50 of 567.13 ± 0.27 µg/mL. All the animals survived the acute toxicity test, with no significant changes in the relative organ weights, suggesting that LD50 is greater than 2000 mg/kg. The animal weights did not vary significantly in the sub-acute toxicity test neither were the alterations in biochemical and hematological tests pronounced, although the histoarchitectures of the kidney, liver and spleen indicated slight anomalies in the evaluated animals. The HPLC analysis revealed the presence of quercetin, ferulic acid, rutin, caffeic acid, morin and gallic acid. CONCLUSIONS: Ethanol leaf extract of Morus mesozygia demonstrated a safe toxicity profile in rodents, supporting its broad folkloric use in African ethnomedicine.

Morus mesozygia leaf extract ameliorates behavioral deficits, oxidative stress and inflammation in Complete Freund's adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus mesozygia Stapf (Moraceae), otherwise referred to as African mulberry, is utilized domestically as a remedy for a variety of inflammatory disorders including rheumatism. AIM: The anti-arthritic effect of the ethylacetate fraction of M. mesozygia leaf extract (EAFMm) was assessed on complete Freund's adjuvant (CFA)-induced arthritis in male Wistar rats. METHOD: Groups of male Wistar rats were injected with CFA (0.2 mL; 10 mg/mL) in the plantar surface of their right hind paws and treated orally with EAFMm (50 and 100 mg/kg) or its vehicle daily for 28 days. The effect on joint inflammation and mechanical nociception threshold, behavioral deficits (spontaneous motor activity in the open field test and depressive-like symptoms in the forced swim test) was evaluated. The levels and activities of the biomarkers of oxidative-nitrosative stress (reduced glutathione, superoxide dismutase, nitrite, and malondialdehyde) and inflammatory markers [TNF-α, IL-6, COX-2, NFκB and myeloperoxidase] were also analysed. RESULTS: The EAFMm at the doses of 50 and 100 mg/kg produced a dose dependent reduction in joint inflammation and mechanical hyperalgesia, and as well improved behavioral deficits like spontaneous motor activity and depressive-like behavior. The EAFMm also significantly reduced oxido-nitrosative stress response in the joint and brain tissues. It also decreased TNF-α, interleukin-6 levels and myeloperoxidase enzyme activities in joints and brain tissues of rats. Furthermore, EAFMm attenuated the activity of NFκB and reduced the cyclooxygenase -2 protein expression level in joint tissues. CONCLUSION: The ethylacetate fraction of Morus mesozygia leaf extract demonstrated anti-arthritic activity and ameliorated co-morbid depressive-like behavior via inhibition of oxidative stress and inflammation in a rat model of arthritis.

Anti-nociceptive and anti-inflammatory activities of ethanol extract and fractions of Morus mesozygia Stapf (Moraceae) leaves and its underlying mechanisms in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus mesozygia Stapf (Moraceae), commonly known as African mulberry, is traditionally used for the treatment of inflammatory disorders such as rheumatism and dermatitis. AIM: This work aimed to evaluate the anti-nociceptive and anti-inflammatory effects of its ethanol (EEMm) extract, and ethylacetate fraction (EAFMm). METHODS: The anti-nociceptive and anti-inflammatory effect of ethanol extracts of M. mesozygia (EEMm), and its ethylacetate (EAFMm) and residual aqueous fraction (RAFMm) was evaluated in hotplate, acetic acid and formalin tests and as well in membrane stabilizing assay and carrageenan-induced paw oedema models. Mechanism of anti-inflammation of EAFMm was investigated in the carrageenan-induced air-pouch model. RESULTS: In the hot plate test of nociception, only the EAFMm showed significant (p < 0.05) anti-nociceptive activity. The extract and fractions significantly reduced number of writhing with EAFMm (400 mg/kg) showing highest inhibition (66.5%) in the acetic acid-induced writhing in mice. EEMm and EAFMm (400 mg/kg) significantly reduced the paw licking time in the early and late phases of the formalin test. The extract and fractions showed good membrane stabilizing activity comparable to indomethacin. EAFMm (100 and 400 mg/kg) showed the highest inhibition of paw oedema (53.4% and 58.1%) in the carrageenan-induced paw oedema model. The EAFMm (100 and 400 mg/kg) reduced exudate volume relative to carrageenan-control (2.64 ± 0.22, 2.08 ± 0.15 vs 3.83 ± 0.18 mL) and neutrophils (8.98 ± 1.36, 8.00 ± 0.22 vs 20.51 ± 1.14) in carrageenan-induced pouch. EAFMm significantly reduced exudate volume, pro-inflammatory cytokines and the expression of COX-2 and NFκB. CONCLUSION: M. mesozygia leaves demonstrated anti-nociceptive and anti-inflammatory activities by suppressing oxidative stress, pro-inflammatory cytokines, cyclooxygenase-2, and nuclear factor kappa B.

Chrysophyllum albidum fruit peel attenuates nociceptive pain and inflammatory response in rodents by inhibition of pro-inflammatory cytokines and COX-2 expression through suppression of NF-κB activation.

Chrysophyllum abidum fruit is a seasonal fruit commonly eaten as snacks with abundant health promoting phytochemicals in the fruit peels. The fruit peels have been reported to be rich in anti-inflammatory eleagnine, myricetin rhamnoside, quercetin, linoleic acid and oleic acid. We hypothesized that the anti-inflammatory effect of the peel extract involve suppression of pro-inflammatory cytokines, cyclooxygenase-2 and nuclear factor-kappa B (NF-κB). Hence, this study was designed to assess the anti-nociceptive and anti-inflammatory effects of fruit peel extract of Chrysophyllum albidum in animal models of nociception and inflammation. The anti-nociceptive activity of CAPEE (100 and 400 mg/kg) was evaluated in acetic acid-induced writhing and formalin-induced paw licking in mice. Formalin-induced paw edema and carrageenan-induced air pouch models of inflammation were used to evaluate the anti-inflammatory activity. CAPEE (100 and 400 mg/kg) significantly reduced abdominal writhing and paw licking in acetic acid and formalin tests in mice, respectively. CAPEE demonstrated significant inhibition of paw edema at 24 h (41.0% and 55.7%) and 72 h (52.3% and 86.6%) after formalin injection. CAPEE suppressed inflammatory responses in carrageenan-induced air pouch by reducing exudates, inflammatory cells infiltration, nitrites and myeloperoxidase activity. There was significant inhibition of tumor necrosis factor-alpha, interleukin-6 levels and reduced immunopositive expression of COX-2 and NF-κB. In conclusion, CAPEE has anti-nociceptive and anti-inflammatory potentials via mechanisms associated with inhibition of pro-inflammatory cytokines and cyclooxygenase-2 (COX-2) expression through suppression of nuclear factor kappa B (NF-κB) activation, and has potential as a functional food ingredient.