Plant Coleus Forskohlii Research Articles

Not all cytochrome b5s are created equal: How a specific CytB5 boosts forskolin biosynthesis in Saccharomyces cerevisiae

Cytochrome B5s, or CytB5s, are small heme-binding proteins, ubiquitous across all kingdoms of life that serve mainly as electron donors to enzymes engaged in oxidative reactions. They often function as redox partners of the cytochrome P450s (CYPs), a superfamily of enzymes participating in multiple biochemical processes. In plants, CYPs catalyze key reactions in the biosynthesis of plant specialized metabolites with their activity dependent on electron donation often from cytochrome P450 oxidoreductases (CPRs or PORs). In eukaryotic microsomal CYPs, CytB5s frequently participate in the electron transfer process although their exact role remains understudied, especially in plant systems. In this study, we assess the role of CytB5s in the heterologous biotechnological production of plant specialized metabolites in yeast. For this, we used as a case-study the biosynthesis of forskolin - a bioactive diterpenoid produced exclusively from the plant Coleus forskohlii. The complete biosynthetic pathway for forskolin is known and includes three CYP enzymes. We reconstructed the entire forskolin pathway in the yeast Saccharomyces cerevisiae, and upon co-expression of the three CytB5s - identified in C. forskohlii transcriptomes - alleviation of a CYP-related bottleneck step was noticed only when a specific CytB5, CfCytB5A, was used. Co-expression of CfCytB5A in yeast, in combination with forskolin pathway engineering, resulted in forskolin production at titers of 1.81 g/L in a bioreactor. Our findings demonstrate that CytB5s not only play an important role in plant specialized metabolism but also, they can interact with precision with specific CYPs, indicating that the properties of CytB5s are far from understood. Moreover, our work highlights how CytB5s may act as indispensable components in the sustainable microbial production of plant metabolites, when their biosynthetic pathways involve CYP enzymes.

Seasonal diversity & spaciotemporal distribution of fungal endophytes associated with the medicinal plant Coleus forskohlii Briq.

Fungi that colonize the healthy tissues of the plants without showing any disease symptoms in the host plants are termed as fungal endophytes. The presence of fungal endophytes provides a positive effect on the host’s growth & development and also triggers the production of some essential bioactive compounds in the host. This study was undertaken to isolate, identify and understand the spaciotemporal distribution and seasonal diversity of fungal endophytes associated with the leaf, stem & root of Coleus forskohlii, an important and endangered medicinal plant. Sampling was done for a period of 12 months between May 2020–April 2021. A total of 950 fungal endophytes were isolated from a total of 1680 tissues of the leaf, stem & root of C. forskohlii. The fungi were identified based on their morphological features and some of them were identified by molecular identification by 18S rRNA sequencing. The endophytic isolates belonged to 10 different orders belonging to 3 different classes-Sordariomycetes (Hypocreales, Xylariales, Microascales, Trichosphaeriales, Glomerellales & Sordariales), Dothiomycetes (Pleosporales, Capnodiales, Botryosphaeriales) & Eurotiomyctes (Eurotiales). About 81.26% of the isolates belonged to Ascomycota & 2.63% of the isolates belonged to Mucoromycota. Chaetomium globosum, Collariella bostrychodes, C. robusta, Colletotrichum gloeosporioides, Fusarium chlamydosporum, Sterile hyaline mycelia, Aspergillus niger, Xylaria curta, X. grammica, Mucor circinelloides & Trichoderma harizianum were the frequently isolated species of fungi. C. globosum, C. bostrychodes, C. gloeosporioides, sterile hyaline mycelia & X. curta were found distributed in all the tissues of the plant. C. forskohlii has thus revealed a rich diversity of fungal endophytes that could be isolated & cultured to yield some pharmacologically important bioactive compounds.

ASSESSMENT OF THE ANTIOXIDANT POWER OF IN VITRO OBTAINED COLEUS FORSKOHLII BRIQ

In thе prеsent studу, a simрle protосоl for in vitro rooting induction of the important medicinal plant Coleus forskohlii Briq with a high content of secondary metabolites with antioxidant activity was described. For the in vitro germination seeds of C. forskohlii were placed on MS medium suррlemented with 0.4 mg L-1 gibberellic acid and 1.0 mg L-1 CaCl2. The оbtаinеd shoots were cultured on a half-strength ½ MS medium containing indole-3-butyric acid (IBA) or indole-3-acetic acid (IAA) at concentrations of 0.1 and 0.5 mg L-1. The maximum rooting of plants (95%) with mean values of 9.2 roots per explant, root length (5.1 cm) and root fresh weight (0.085 g) was obtained on half-strength MS medium with 0.1 mg L-1 IAA after three weeks of culture. The plants were successfully ex vitro adapted with 93.3% survival on the mixture substrate of soil, peat and sand (2:1:1 v/v/v). The antioxidant enzymes асtivitiеs (superoxide dismutase, catalase, ascorbate peroxidase and guaiacol peroxidase) showed the highest values when IBA was used for C. forskohlii in vitro cultivation. Applied auxins influenced the level of secondary metabolites synthesis. Half strength MS culture medium supplemented with 0.5 mg L-1 IAA caused the highest total phenol and flavonoid content as well as the highest antioxidant activity level (radical scavenging activity and ferric reducing antioxidant power). The results indiсаte thаt orgаnоgenеsis is а very соmplicated biologiсаl prосеss involving up and downregulation of plant enzyme and non-enzyme antioxidant protection systems, which plау an imроrtant role during the organogenesis of plants.

ASSESSMENT OF THE ANTIOXIDANT POWER OF IN VITRO OBTAINED COLEUS FORSKOHLII BRIQ

In thе prеsent studу, a simрle protосоl for in vitro rooting induction of the important medicinal plant Coleus forskohlii Briq with a high content of secondary metabolites with antioxidant activity was described. For the in vitro germination seeds of C. forskohlii were placed on MS medium suррlemented with 0.4 mg L-1 gibberellic acid and 1.0 mg L-1 CaCl2. The оbtаinеd shoots were cultured on a half-strength ½ MS medium containing indole-3-butyric acid (IBA) or indole-3-acetic acid (IAA) at concentrations of 0.1 and 0.5 mg L-1. The maximum rooting of plants (95%) with mean values of 9.2 roots per explant, root length (5.1 cm) and root fresh weight (0.085 g) was obtained on half-strength MS medium with 0.1 mg L-1 IAA after three weeks of culture. The plants were successfully ex vitro adapted with 93.3% survival on the mixture substrate of soil, peat and sand (2:1:1 v/v/v). The antioxidant enzymes асtivitiеs (superoxide dismutase, catalase, ascorbate peroxidase and guaiacol peroxidase) showed the highest values when IBA was used for C. forskohlii in vitro cultivation. Applied auxins influenced the level of secondary metabolites synthesis. Half strength MS culture medium supplemented with 0.5 mg L-1 IAA caused the highest total phenol and flavonoid content as well as the highest antioxidant activity level (radical scavenging activity and ferric reducing antioxidant power). The results indiсаte thаt orgаnоgenеsis is а very соmplicated biologiсаl prосеss involving up and downregulation of plant enzyme and non-enzyme antioxidant protection systems, which plау an imроrtant role during the organogenesis of plants.

Isoforskolin, an adenylyl cyclase activator, attenuates cigarette smoke-induced COPD in rats

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by limited airflow due to pulmonary and alveolar abnormalities from exposure to cigarette smoke (CS). Current therapeutic drugs are limited and the development of novel treatments to prevent disease progression is challenging. Isoforskolin (ISOF) from the plant Coleus forskohlii is an effective activator of adenylyl cyclase (AC) isoforms. Previously we found ISOF could attenuate acute lung injury in animal models, while the effect of ISOF on COPD has not been elucidated. PurposeIn this study, we aimed to evaluate the efficacy of ISOF on COPD and reveal its potential mechanisms. MethodsA rat model of COPD was established by long-term exposure to CS, then the rats were orally administered with ISOF (0.5, 1 and 2 mg/kg). The pulmonary function, lung morphology, inflammatory cells and cytokines in serum or bronchoalveolar lavage fluid (BALF) were evaluated. Transcriptomics, proteomics and network pharmacology analysis were utilized to identify potential mechanisms of ISOF. Droplet digital PCR was used to detect the mRNA expression of AC1-10 in donor lung tissues. AC activation was determined in recombinant human embryonic kidney 293 (HEK293) cells stably expressing human AC isoforms. In addition, ISOF caused trachea relaxation ex vivo were assessed in isolated trachea rings from guinea pigs. ResultsISOF significantly ameliorated pathological damage of lung tissue and improved pulmonary function in COPD rats. ISOF treatment decreased the number of inflammatory cells in peripheral blood, and also the levels of pro-inflammatory cytokines in serum and BALF. Consistent with omics-based analyses, ISOF markedly downregulated the mTOR level in lung tissue. Flow cytometry analysis revealed that ISOF treatment reduced the ratio of Th17/Treg cells in peripheral blood. Furthermore, the expression levels of AC1 and AC2 are relatively higher than other AC isoforms in normal lung tissues, and ISOF could potently activate AC1 and AC2 in vitro and significantly relax isolated guinea pig trachea. ConclusionCollectively, our studies suggest that ISOF exerts its anti-COPD effect by improving lung function, anti-inflammation and trachea relaxation, which may be related to AC activation, mTOR signaling and Th17/Treg balance.

Isoforskolin Alleviates AECOPD by Improving Pulmonary Function and Attenuating Inflammation Which Involves Downregulation of Th17/IL-17A and NF-κB/NLRP3.

Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, is widely considered to be related to cigarette smoke (CS), and viral infections trigger acute exacerbation of COPD (AECOPD). Isoforskolin (ISOF) is a bioactive component from the plant Coleus forskohlii, native to Yunnan in China. It has been demonstrated that ISOF has anti-inflammatory effect on acute lung injury animal models. In the present study, we investigated the efficacy and mechanism of ISOF for the prevention and treatment of AECOPD. Mice were exposed to CS for 18 weeks and then infected with influenza virus A/Puerto Rico/8/34 (H1N1). ISOF (0.5, 2 mg/kg) was intragastrically administered once a day after 8 weeks of exposure to cigarette smoke when the body weight and lung function of model mice declined significantly. The viral load, pulmonary function, lung morphology, Th17 cells, and inflammatory cytokines in lung tissues were evaluated. The expression of nuclear factor κB (NF-κB) and NOD-like receptor pyrin domain–containing protein 3 (NLRP3) inflammasome pathways were detected. The results showed that ISOF treatment reduced the viral load in the lung homogenate, decreased the lung index of model mice, and lung pathological injuries were alleviated. ISOF also improved the pulmonary function with increased FEV0.1/FVC and decreased Rn and Rrs. The levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17A, MCP-1, MIG, IP-10, and CRP) in the lung homogenate were reduced after ISOF treatment. ISOF decreased the proportion of Th17 cells in the lung tissues by the flow cytometry test, and the protein expression levels of RORγt and p-STAT3 were also decreased. Furthermore, ISOF significantly inhibited the activation of NF-κB signaling and NLRP3 inflammasome in the lung tissues of model mice. In conclusion, ISOF alleviates AECOPD by improving pulmonary function and attenuating inflammation via the downregulation of proinflammatory cytokines, Th17/IL-17 A, and NF-κB/NLRP3 pathways.

Isoforskolin and forskolin attenuate lipopolysaccharide-induced inflammation through TLR4/MyD88/NF-κB cascades in human mononuclear leukocytes.

The principal active component of isoforskolin (ISOF) is from the plant Coleus forskohlii, native to China, which has attracted much attention for its biological effects. We hypothesize that ISOF and forskolin (FSK) pretreatment attenuates inflammation induced by lipopolysaccharide (LPS) related to toll‐like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B (NF‐κB) signaling. Mononuclear leukocytes (MLs) from healthy donors' blood samples were separated by using density gradient centrifugation. Protein levels of TLR4, MyD88, and NF‐κB were detected using western blot and inflammatory cytokines interleukin (IL) 1β, IL‐2, IL‐6, IL‐21, IL‐23, tumor necrosis factor (TNF) α, and TNF‐β were tested by enzyme‐linked immunosorbent assay and Quantibody array in MLs. Our results showed that LPS augmented the protein levels of TLR4, MyD88, and NF‐κB in MLs and the production of IL‐1β, IL‐2, IL‐6, IL‐21, IL‐23, TNF‐α, and TNF‐β in supernatants of MLs. Despite treatment with ISOF and FSK prior to LPS, the protein levels of TLR4, MyD88, NF‐κB, IL‐1β, IL‐2, IL‐6, IL‐21, IL‐23, TNF‐α, and TNF‐β in MLs were apparently decreased. roflumilast (RF) and dexamethasone (DM) had a similar effect on MLs with ISOF and FSK. Our results, for the first time, have shown that ISOF and FSK attenuate inflammation in MLs induced by LPS through down‐regulating protein levels of IL‐1β and TNF‐α, in which TLR4/MyD88/NF‐κB signal pathway could be involved.

Forskolin Modulate Silent Information Regulator 1 (SIRT1) gene Expression and Halts Experimentally-Induced Acute Kidney Injury

Acute kidney injury is a very serious medical condition; change of the normal physiological oxidant-antioxidant balance has been reported as a major cause for renal injury. Silent information regulator 1 (Sirt1) is a nicotinamide adenine dinucleotide- (NAD+-) dependent deacetylase that has nephro-protective effect against ischemia or injury by toxic substances by increasing cell resistance to oxidative stress. Forskolin is derived from plant Coleus forskohlii and has been used to treat the heart disease, hypertension, diabetes and asthma. This study was done to investigate the possible protective role of forskolin against glycerol- induced acute nephrotoxicity and also to study the possible mechanisms underlying this action. In the present study rats were randomly divided into four groups. Rats in the control group received distilled water orally for 15 days, four days before scarification they received half the dose of saline (10 ml/kg) in each hind limb muscle; rats in the FSK group received 500 mg/kg per day, orally for 15 days; those in the glycerol group (AKI) received half the dose of glycerol (10 ml/kg, 50% v/v in sterile saline) in each hind limb muscle; rats in the FSK + glycerol (AKI) group received FSK 500 mg/kg per day, orally 12 days before glycerol injection and continued for three days after glycerol administration with a total period of 15 days, all rats were deprived of water for 24 h before glycerol injection. Parameters tested in this study were kidney function tests (urea, creatinine), oxidative stress parameters (MDA, GST), anti-inflammatory marker (TNF-α), anti-apoptotic marker (caspase-3), SIRT gene expression detected by RT-PCR and histopathlogical study. Results: Glycerol administration caused significant increase in all tested parameters except SIRT gene expression which decreased with glycerol administration. Pretreatment with forskolin caused significant decrease of levels of urea, creatinine, MDA, TNF-α and also decreased activity of caspase-3 and GST, with significant improvement of SIRT expression. Histopathological examination revealed that the glycerol caused severe kidney damage in the form of hemorrhage, inflammatory cell infiltration and intra-tubular cast formation compared to normal renal histology and architecture of the control and forskolin groups. Forskolin pretreatment of glycerol induced AKI caused marked improvement of histological picture which exhibited mild edema and tubular vacuolization compared to the control group. In conclusion the possible beneficial effect of forskolin in protection against nephrotoxicity is due to its ability to modulate the disrupted expression of SIRT gene as well as its anti-oxidant, anti-inflammatory and anti-apoptotic properties. This may open a new therapeutic window for renal patient.

Evaluation of phytochemical screening of Coleus forskohlii L. leaf extract

Coleus forskohlii L. plant Extract is derived from roots and leaves from Coleus forskohlii. Coleus is used in India and China folk medicines and is a traditional digestive remedy. Currently this plants levees and roots are extensively cultivated is Southern and western India. Forskohlii helps to lower blood pressure, dilates the blood vessels. Traditionally claimed to be constructive in the cure of cutaneous affections such as scabies, guinea worm, eczema and herpetic diseases. Conversely, there are no customary scientific reports for its antipsoriatic activity. Hence, the plant Coleus forskohlii has been chosen to establish scientific data for its traditional claim as anti-cancer. In the present study a chemical test performed against the, all the phytochemical constituents for their preliminary screening of each solvent extract of leaf like water, methanol, chloroform, ethyl acetate, and acetone. From the phytochemical investigation of the leaf extracts; the result is revealed the presence of carbohydrates, glycosides, tannins, flavonoids, triterpenoids, and lipids in all the solvent extracts. But phenols are more retain in methanolic leaf extract remain all the phytochemical constituents.

Forskolin protects against cisplatin-induced ototoxicity by inhibiting apoptosis and ROS production

Cisplatin is widely used in the treatment of various types of cancer. However, it could cause severe side effects such as ototoxicity, which greatly limit the clinical application of cisplatin. Forskolin (FSK) is a diterpene derived from the plant Coleus forskohlii, and has been proven an effective drug for cardiovascular disease, diabetes, and asthma because of its anti-oxidant and anti-inflammatory action. Here, we investigated the effects of FSK in cisplatin-induced ototoxicity, and we found that FSK could significantly protect against cisplatin-induced ototoxicity in both cell line and isolated mouse cochlear. Pretreatment of FSK attenuated cisplatin-induced hearing loss especially at high frequency regions. FSK inhibited the activation of mitochondrial apoptotic pathway as well as reactive oxygen species (ROS) production. Moreover, we identified PKA and MAPK signaling pathway which may be connected with the protective effect of FSK. Our study provided the first evidence that FSK may be used as a drug to weaken the ototoxicity induced by cisplatin.

Isoforskolin downregulates proinflammatory responses induced by Borrelia burgdorferi basic membrane protein A.

The plant Coleus forskohlii is distributed primarily in India, Thailand, China, Egypt and Brazil and has a history of use in the treatment of multiple diseases. Isoforskolin (ISOF) is the principle active component of C. forskohlii native to China and has previously been studied for its biological effects. The aim of the present study was to evaluate the effect of ISOF on the proinflammatory responses induced by recombinant Borrelia burgdorferi basic membrane protein A (rBmpA). In in vitro experiments, the proinflammatory effects of rBmpA and the anti-inflammatory function of ISOF were evaluated in murine macrophages, human macrophages and dendritic cells by detecting the transcription and expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. In in vivo experiments, mean arthritis index and X-ray and histopathological examinations were used to verify the role of ISOF in experimental Lyme arthritis in mice. The results indicated that rBmpA, which induced the transcription and expression of TNF-α and IL-6, activated proinflammatory responses in murine macrophages, human macrophages and dendritic cells. In turn, ISOF downregulated the transcription and expression of TNF-α and IL-6 induced by rBmpA. Additionally, the in vivo experiments demonstrated that ISOF could also inhibit the symptoms of experimental Lyme arthritis. These results suggest that ISOF may have a potential application as an anti-inflammatory agent for the treatment of Lyme arthritis.

Total biosynthesis of the cyclic AMP booster forskolin from Coleus forskohlii.

Forskolin is a unique structurally complex labdane-type diterpenoid used in the treatment of glaucoma and heart failure based on its activity as a cyclic AMP booster. Commercial production of forskolin relies exclusively on extraction from its only known natural source, the plant Coleus forskohlii, in which forskolin accumulates in the root cork. Here, we report the discovery of five cytochrome P450s and two acetyltransferases which catalyze a cascade of reactions converting the forskolin precursor 13R-manoyl oxide into forskolin and a diverse array of additional labdane-type diterpenoids. A minimal set of three P450s in combination with a single acetyl transferase was identified that catalyzes the conversion of 13R-manoyl oxide into forskolin as demonstrated by transient expression in Nicotiana benthamiana. The entire pathway for forskolin production from glucose encompassing expression of nine genes was stably integrated into Saccharomyces cerevisiae and afforded forskolin titers of 40 mg/L.

HEPATOPROTECTIVE EFFECT OF FORSKOLIN IN CARBON TETRACHLORIDE-INDUCED MODEL OF ACUTE LIVER INJURY

Liver disease is one of the most common causes of death in the world. Nowadays, research studies have been focused on the development of new drugs for treatment of liver damage. Some natural products from medicinal plants have been found as potent agents for protection against liver injury induced by chemicals. Thus, it is interesting to find more effective natural products for protection against liver injury. Accordingly, the present study was designed to assess the hepatoprotective potential of a diterpenoid forskolin, isolated from the Indian plant Coleus forskohlii, at different doses in rat model with acute liver injury induced by carbon tetrachloride (CCl4) at a dose of 1ml/kg intraperitoneally as a mixture with corn oil. Forkolin was administered in doses of 5,10,20,40 mg/kg intraperitoneally for 7 days. Its protective effect was assessed via liver function tests and histopathological liver sections. Significant reduction in the hepatic enzymes levels was found in animals treated with forskolin at a dose of 10mg/kg as well as restoration of hepatocellular architecture. Therefore, treatment with forskolin showed preventive effect against CCl4-induced liver damage.

Effect of Chronic Administration of Forskolin on Glycemia and Oxidative Stress in Rats with and without Experimental Diabetes

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant.

Cutaneous Pigmentation in Health and Disease: Novel and Well-Established Players

Cutaneous pigment formation and aberration in disease are addressed. Dynoodt et al. (this issue) present data on a specific micro RNA that downregulates proteins involved in melanogenesis and melanosome movement. Kim et al. (this issue) present data showing that Wnt signaling is involved in the pathogenesis of melasma. Both articles enhance our understanding of cutaneous pigmentation and point to targets in the development of novel therapeutic modalities.

Coleusin factor exerts cytotoxic activity by inducing G 0/G 1 cell cycle arrest and apoptosis in human gastric cancer BGC-823 cells

Coleusin factor (CF), a kind of diterpenoids, is isolated and purified from the root of a Chinese tropical plant Coleus forskohlii by our laboratory. Our previous studies have demonstrated that CF significantly inhibits growth in some kinds of cancer cell lines. Here, we found that CF remarkably inhibited growth in human gastric cancer BGC-823 cells by decreasing cell proliferation, inducing G 0/G 1 cell cycle arrest and apoptosis. CF also decreased the mitochondrial membrane potential in BGC-823 cells. Immunoblotting analysis revealed that CF significantly decreased the expressions of cyclinD1, Bcl-2, and Bcl-x L, increased the expressions of cytosol cytochrome c, p53, p21, and Rb. In addition, CF significantly increased the expressions and activities of caspase-3 and -9. More importantly, CF potently inhibited the growth of BGC-823 cells xenografted in athymic nude mice with negligible body weight loss and damage towards the spleen. These results indicate that CF exerts a cytotoxic effect on BGC-823 cells by inducing cell cycle arrest and apoptosis.

Identification of a Forskolin-Like Molecule in Human Renal Cysts

Renal cyst enlargement is increased by adenosine cAMP, which is produced within mural epithelial cells. In a search for modulators of cAMP synthesis cyst fluids from 18 patients with autosomal dominant or recessive polycystic kidney disease (PKD) were analyzed, and in 15 of them, a stable lipophilic molecule that increased cAMP levels, stimulated transepithelial chloride and fluid secretion, and promoted the proliferation of human cyst epithelial cells was characterized. With the use of HPLC-mass spectrometry, a bioactive lipid with the same mass spectral fingerprint, the same chromatographic retention time, and the same biologic properties as forskolin, a widely known, potent adenylyl cyclase agonist, has been isolated and identified within the cyst fluid. Forskolin is synthesized by the plant Coleus forskohlii, but its appearance or compounds like it have not been reported in animals. The origin of forskolin in patients with PKD was not revealed by this study. Synthesis by mural cyst epithelial cells or an exogenous source are the most likely possibilities. Forskolin is sold for weight management and as a cardiovascular tonic in health stores and through the Worldwide Web. It is concluded that forskolin may have a role in promoting the enlargement of cysts in autosomal dominant PKD and recommended that patients avoid oral and parenteral preparations that contain this compound.

Molecular and crystal structure of Coleonol-B, C22H34O7*

Abstract Coleonol-B a diterpenoid isolated from the roots of the Indian plant Coleus forskohlii crystallizes in the orthorhombic system, space group P212121 with a = 29.085(5), b = 11.603(2), c = 6.341(1) Å and four molecules in the unit cell. As in Coleonol, the substituents at the 6- and 7-positions are in the β-configuration. 2133 reflections were used, 398 parameters were refined. Final R-values were Rw = 0.057 and R = 0.045.

Forskolin, a new inotropic agent

Forskolin is a labdane diterpene obtained from the plant Coleus Forskohlii. Forskolin probably acts by activation of adenylcylase. Forskolin was infused intravenously in patients with low cardiac output, commencing with 0.1 ug/kg/minute in Hemaccel solution. The rate was doubled every 2 minutes to a maximum of 1.6 ug/kg/Min. Ventricular functions was evaluated by a nuclear stethoscope before infusion and 5, 10, 15 and 50 Minutes after stopping the infusion. The cardiovascular parameters included heart rate, systolic blood pressure, diastolic blood pressure, ejection fraction, cardiac output, peak ejection rate, peak filling time and overall filling time. The ejection fraction, in 8 patients, rose from the mean basal value of 23.10± 2037 to 38±3.59(P< 0.001). There were also significant increases in ejection velocity and filling velocity. These effects were seen at a dose of 8–16 ug/kg/10 minutes. No significant chronotropic or barotropic effects were notedo Forskolin was extremely well tolerated at this dose.

Molecular and crystal structure of Coleonol, C22H34O7

Coleonol isolated from the Indian plant Coleus Forskohlii crystallizes in space group P 2 1 2 1 2 1 with four molecules in the unit cell. The doubt regarding the identity of Coleonol with Forskolin has been clarified.