From NSAIDs to Glucocorticoids and Beyond

Our interest in inflammation and its treatment stems from ancient times. Hippocrates used willow bark to treat inflammation, and many centuries later, salicylic acid and its derivative aspirin’s ability to inhibit cyclooxygenase enzymes was discovered. Glucocorticoids (GC) ushered in a new era of treatment for both chronic and acute inflammatory disease, but their potentially dangerous side effects led the pharmaceutical industry to seek other, safer, synthetic GC drugs. The discovery of the GC-inducible endogenous anti-inflammatory protein annexin A1 (AnxA1) and other endogenous proresolving mediators has opened a new era of anti-inflammatory therapy. This review aims to recapitulate the last four decades of research on NSAIDs, GCs, and AnxA1 and their anti-inflammatory effects.

Ultrasonic or Microwave Cascade Treatment of Medicinal Plant Waste

In this study, we present a strategy for valorizing lignocellulosic wastes (licorice root and willow bark) that result from industrial extraction of active principles using water as green solvent and aqueous NaOH solution. The wastes were submitted to severe ultrasound (US) and microwave (MW) treatments. The aim of these treatments was to extract the remaining active principles (using water as a solvent) or to prepare them for cellulose enzymatic hydrolysis to hexoses (performed in an NaOH aqueous solution). The content of glycyrrhizic acid and salicin derivatives in licorice root and willow bark wastes, respectively, were determined. The best results for licorice root were achieved by applying the US treatment for 5 min at 25 °C (26.6 mg glycyrrhizic acid/gDM); while, for willow bark, the best results were achieved by applying the MW treatment for 30 min at 120 °C (19.48 mg salicin/gDM). A degradation study of the targeted compounds was also performed and showed good stability of glycyrrhizic acid and salicin derivatives under US and MW treatments. The soluble lignin concentration prior to enzymatic hydrolysis, as well as the saccharide concentration of the hydrolyzed solution, were determined. As compared with the MW treatment, the US treatment resulted in saccharides concentrations that were 5% and 160% higher for licorice root and willow bark, respectively.

Anti-cancer agents from natural sources: A review

The natural products have played a dominant role in the treatment of human ailments. The discovery of penicillin has changed the scenario of modern medicine. With the ancient use of quinine for malaria, willow bark for pain and several other natural products used as medicines in ancient system of medicine such as Ayurveda and traditional China, the discovery of the medicines for the allopathic use from natural source has gained substantial attention. The ancient system of Ayurveda describes the used of many plants extracts being used for the treatment of cancer. Prevailing epidemiological factors have also described the use of the msediterranean diet and inclusion of fruits and vegetables to score low as risk factor for the cancers. Further the several discoveries have led to the transformation of the active constituents of the natural products from the dietary sources for the chemoprevention. Substantial trials in the development of the drugs from the marine and microbial origin have been fruitful and positive to develop safe and efficacious drugs. However, the success being very low due to unavailability of natural products in large gram amounts required for the clinical trials. The total synthesis of m any natural products from marine origin has also emerged to solve this issue and led to successful development of 4 marine drugs as anti-cancer agents. This overview reviews the anticancer drugs from the natural origin as the chemo preventive and chemotherapeutic agents. Wherever possible the details of the clinical trials have been discussed along with uses and mechanism of action.

Identification of Salicylates in Willow Bark (Salix Cortex) for Targeting Peripheral Inflammation

Salix cortex-containing medicine is used against pain conditions, fever, headaches, and inflammation, which are partly mediated via arachidonic acid-derived prostaglandins (PGs). We used an activity-guided fractionation strategy, followed by structure elucidation experiments using LC-MS/MS, CD-spectroscopy, and 1D/2D NMR techniques, to identify the compounds relevant for the inhibition of PGE2 release from activated human peripheral blood mononuclear cells. Subsequent compound purification by means of preparative and semipreparative HPLC revealed 2′-O-acetylsalicortin (1), 3′-O-acetylsalicortin (2), 2′-O-acetylsalicin (3), 2′,6′-O-diacetylsalicortin (4), lasiandrin (5), tremulacin (6), and cinnamrutinose A (7). In contrast to 3 and 7, compounds 1, 2, 4, 5, and 6 showed inhibitory activity against PGE2 release with different potencies. Polyphenols were not relevant for the bioactivity of the Salix extract but salicylates, which degrade to, e.g., catechol, salicylic acid, salicin, and/or 1-hydroxy-6-oxo-2-cycohexenecarboxylate. Inflammation presents an important therapeutic target for pharmacological interventions; thus, the identification of relevant key drugs in Salix could provide new prospects for the improvement and standardization of existing clinical medicine.

Doron medicum—the gift of medicine: How a rare 17th century medical translation positively impacted the community and predicted current analgesic techniques

In 1683, a self-proclaimed apothecary physician and London professor of physick by the name of Guilelmus (William) Salmon authored a pharmacopoeia titled Doron medicum, the ‘gift of medicine’ (Greek/Latin translation). This text formulates an English supplement to the Latin Materia medica (16th century), discussing internal and external compound medicines of the late 17th century. This pharmacopoeia enabled those incapable of reading Latin to provide medical care to a challenging post-plague community. Opiology, mercury, dragon’s blood, willow bark, animal preparations and therapies now considered obscure, provide insight into therapies at the time. Early critical care treatments in haemorrhage control and pain management are described. Doron medicum preceded the controversial opening by the College of Physicians of the first London Dispensary in 1698, and was published in a maturing period of medical governance and healthcare establishment in London. During the 17th century, great competition and debate existed between the Royal College of Physicians and the apothecaries. Throughout such debates, William Salmon advocated for access to medical care for the poor and recognition of an allied approach to healthcare. This paper discusses Salmon’s contribution to medicine, which has been poorly transcribed in medical history. A selection of opiate-based analgesic therapies, early critical care strategies and animal preparations are revisited. A small chronicle of William Salmon’s life and professional achievements will be reviewed. Debate surrounding the opening of the first London Dispensary will be discussed in relation to William Salmon’s contribution, echoing ongoing contemporary challenges in healthcare over 300 years later.

Bioactive Films from Willow Bark Extract and Nanocellulose Double Network Hydrogels

In nature, the protection of sensitive components from external threats relies on the combination of physical barriers and bioactive secondary metabolites. Polyphenols and phenols are active molecules that protect organisms from physical and chemical threats such as UV irradiation and oxidative stress. The utilization of biopolymers and natural bioactive phenolic components as protective coating layers in packaging solutions would enable easier recyclability of materials and greener production process compared with the current plastic-based products. Herein, we produce a fully wood-based double network material with tunable bioactive and optical properties consisting of nanocellulose and willow bark extract. Willow bark extract, embedded in nanocellulose, was cross-linked into a polymeric nanoparticle network using either UV irradiation or enzymatic means. Based on rheological analysis, atomic force microscopy, antioxidant activity, and transmittance measurements, the cross-linking resulted in a double network gel with enhanced rheological properties that could be casted into optically active films with good antioxidant properties and tunable oxygen barrier properties. The purely biobased, sustainably produced, bioactive material described here broadens the utilization perspectives for wood-based biomass, especially wood-bark extractives. This material has potential in applications where biodegradability, UV shielding, and antioxidant properties of hydrogels or thin films are needed, for example in medical, pharmaceutical, food, and feed applications, but also as a functional barrier coating in packaging materials as the hydrogel properties are transferred to the casted and dried films.

Seed Treatment with Biostimulants Extracted from Weeping Willow (Salix babylonica) Enhances Early Maize Growth

Biostimulants can be used as innovative and promising agents to address current needs of sustainable agriculture. Weeping willow tree (Salix babylonica) extracts are rich in many bioactive compounds, including, but not limited, to salicylates and phenolics. In this study, the potential of willow bark (WB) and willow leaf (WL) extracts is evaluated as plant-based biostimulants to improve the early growth of maize (Zea mays) under control and salinity stress conditions. In 3 days, seed treatment with salicylic acid and willow extract increased the shoot FW of maize seedlings 130% and 225%, respectively. The root area was, on average, enhanced by 43% with SA and 87% with willow extract applications. Moreover, these extracts increased the leaf protein concentration and reduced the negative effects of salinity during early growth. Reductions in lipid peroxidation and specific activities of antioxidative enzymes by seed treatments with willow extracts suggests a mitigation of salinity-induced oxidative stress. For most reported traits, WL applications were at least as effective as WB applications. Results indicate that aqueous extracts of weeping willow leaves, as well as bark, can be used as seed treatment agents with biostimulant activity to improve seedling growth and establishment under control and stress conditions.

The Role of Organic Small Molecules in Pain Management

In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the chemical features of the different small organic molecules that have been used in pain management will be studied. Then, the mechanism of different types of pain will be assessed, including neuropathic pain, inflammatory pain, and the relationship found between oxidative stress and pain. This will include obtaining insights into the cyclooxygenase action mechanism of nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and etoricoxib and the structural difference between the two cyclooxygenase isoforms leading to a selective inhibition, the action mechanism of pregabalin and its use in chronic neuropathic pain, new theories and studies on the analgesic action mechanism of paracetamol and how changes in its structure can lead to better characteristics of this drug, and cannabinoid action mechanism in managing pain through a cannabinoid receptor mechanism. Finally, an overview of the different approaches science is taking to develop more efficient molecules for pain treatment will be presented.