A review on herbal antiasthmatics

In traditional systems of medicine, many plants have been documented to be useful for the treatment of various respiratory disorders including asthma. In the last two decades the use of medicinal plants and natural products has been increased dramatically all over the world. Current synthetic drugs used in pharmacotherapy of asthma are unable to act at all the stages and targets of asthma. However some herbal alternatives employed in asthma are proven to provide symptomatic relief and assist in the inhibition of disease progression also. The herbs have shown interesting results in various target specific biological activities such as bronchodilation, mast cell stabilization, anti-anaphylactic, anti-inflammatory, anti-spasmodic, anti-allergic, immunomodulatory and inhibition of mediators such as leukotrienes, lipoxygenase, cyclooxygenase, platelet activating, phosphodiesterase and cytokine, in the treatment of asthma. This paper is an attempt to classify these pharmacological and clinical findings based on their possible mechanism of action reported. It also signifies the need for development of polyherbal formulations containing various herbs acting at particular sites of the pathophysiological cascade of asthma for prophylaxis as well as for the treatment of asthma

Optimization of the Antitumor Activity of Sequence-specific Pyrrolobenzodiazepine Derivatives Based on their Affinity for ABC Transporters

Pyrrolobenzodiazepine (PBD) derivatives are highly potent sequence-specific DNA cross-linking agents. The present study aimed to identify key physicochemical properties influencing the interaction of a series of PBDs (four dimers and 12 monomers) with the three major human ATP-binding cassette (ABC) transporters (P-gp, ABCG2, and MRP1). Isogenic cell lines expressing P-gp and ABCG2, cell lines with acquired resistance to cytotoxic agents due to the high expression of ABC transporters, and specific inhibitors against P-gp, ABCG2, and MRP1 were used. P-gp and ABCG2 decreased the permeability of the PBD dimers across cell membranes and their interaction with DNA, reducing DNA damage and the overall cytotoxic effect. PBD monomer SG-2823 formed a conjugate with glutathione and interacted with MRP1, reducing its cytotoxic effect in A549 cells. Structure–activity relationship revealed that the interaction of PBDs with the transporters could be predicted considering the molecular weight, the lipophilicity, the number of (N + O) atoms and aromatic rings, the polar surface area, the hydrogen bonding energy, and electrophilic centers. A rational design of novel PBDs with increased potency and reduced interaction with the ABC transporters is proposed