Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice.

Fibromyalgia (FM) is an idiopathic disorder characterized by generalized pain and associated symptoms such as depression and anxiety. Cannabis sativa shows different pharmacological activities, such as analgesic, anti-inflammatory, neuroprotective, and immunomodulatory. Associated with this, the use of an oil with low concentrations of THC can reduce the psychomimetic adverse effects of the plant. Therefore, the present study aimed to evaluate the analgesic effect of broad-spectrum cannabis oil with low THC concentration in an experimental model of FM. Mechanical hyperalgesia, thermal allodynia, depressive- and anxious-related behavior, and locomotor activity were evaluated after reserpine (0.25 mg/kg; injected subcutaneously (s.c.) once daily for three consecutive days) administration. Our results showed that oral administration of broad-spectrum cannabis oil (0.1, 1, and 3 mg/kg, p.o.) in a single dose on the 4th day inhibited mechanical hyperalgesia and thermal allodynia induced by reserpine. Relevantly, treatment during four days with broad-spectrum cannabis oil (0.1 mg/kg, p.o.) reduced mechanical hyperalgesia 1 h after reserpine administration. Intraplantar treatment with cannabis oil significantly reversed mechanical and heat thermal nociception induced by reserpine injection. Interestingly, spinal and supraspinal administration of broad-spectrum cannabis oil completely inhibited mechanical hyperalgesia and thermal sensitivity induced by reserpine. The repeated cannabis oil administration, given daily for 14 days, markedly mitigated the mechanical and thermal sensitivity during the FM model, and its reduced depressive-like behavior induced by reserpine. In summary, broad-spectrum cannabis oil is an effective alternative to reverse the reserpine-induced fibromyalgia model.

Buffalo Milk Whey Activates Necroptosis and Apoptosis in a Xenograft Model of Colorectal Cancer.

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.