Modern Research Progress Of Clerodendranthus Spicatus And Its Active Extracts in Treatment Of Kidney Related Diseases

Abstract: Kidney-related-disease is a general name of a series of common clinical diseases, including kidney stones, gouty nephropathy,diabetes nephropathy, renal failure, nephrotic syndrome, etc. The main clinical manifestations are proteinuria, hematuria, edema, hypertension, and other symptoms. At present, western medicine is mainly used in the treatment of these kinds of diseases, with many side effects and poor curability. Cleodendranthus spicatus, a commonly used herbal medicine of Zhuang, Dai, and other ethnic minorities in China, possesses the marks of diuresis, stone excretion, anti-inflammatory, and regulating renal functions. A large number of folk application experiences showed that it owned magical curative effects on kidney-related diseases without toxic and side effects. This paper systematically combed and summarized the modern pharmacological effects. Clinical research progresses of C. spicatus extracts and its active components, in order to provide a reference for deeper research on its pharmacological mechanisms and clinical applications in the treatments of kidney diseases.

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Keywords: Cleodendranthus spicatus (Thunb.) C. Y. Wu; Mao Xu Cao; renal calculus; kidney; mechanisms of action

 

Kidney-related diseases are chronic diseases with a long course [1] and are characterized by insidious onset, complexity, and intractability [2], mainly including kidney stones, gouty nephropathy, diabetic nephropathy, renal failure, and nephrotic syndrome. Kidney stones are caused by the abnormal accumulation of crystalline material (e.g., calcium oxalate, calcium urate, etc.) in the kidney, which is clinically manifested by the formation of stones of a certain size in the renal pelvis or calyces [3]. During an attack, patients will show symptoms such as severe urinary pain, urinary urgency, and hematuria. Gouty nephropathy is kidney damage caused by the accumulation of uric acid in the body to form hyperuricemia, which mainly manifests as proteinuria, hematuria, and edema [4].

Diabetic nephropathy refers to chronic kidney disease caused by diabetes [5], and the damage is mainly manifested by glomerular thylakoid hyperplasia, basement membrane thickening, and glomerulosclerosis [6], and its main clinical manifestation is proteinuria. Renal failure is clinically divided into acute renal failure, which is caused by a sudden decrease in glomerular filtration function resulting in the retention of body wastes and disturbance of acid-base and electrolyte balance [7], and chronic renal failure, which is caused by the long-term persistent effects of multiple kidney-related chronic diseases such as glomerulonephritis and hereditary nephritis, manifesting as disturbance of acid-base balance and cardiovascular and respiratory disorders [8]. Most patients eventually develop end-stage renal disease, which is life-threatening. Nephrotic syndrome is a syndrome caused by increased permeability of the glomerular basement membrane resulting in large amounts of proteinuria [9], which mainly manifests clinically as proteinuria and edema, with edema manifestations mainly in the face and lower limbs in mild cases and plasma cavity effusion in severe cases, which can cause a variety of complications and threaten the life of patients if not treated in a timely manner [10]. Kidney tea, also known as Cistanche, is a traditional Chinese herb with a long history of folk application, and is the dried above-ground part of Kidney tea, family Labiatae, widely distributed in Xinjiang, Gansu, and Inner Mongolia, China [11], and also in the Middle East and Central Asia [12]. Kidney tea is bitter and cool in nature, and can be used alone or in combination, with diuretic and stone removal, uric acid lowering and anti-inflammatory effects [12]. It has been used in folklore for the treatment of kidney stones, gout nephropathy, diabetic nephropathy, etc. [13]. It is effective in the treatment of kidney stones, gout nephropathy, diabetic nephropathy, and other kidney-related diseases.
The main chemical components of kidney tea are flavonoids, phenolic acids, terpenoids, volatile oils, etc. [14]. The main chemical components of kidney tea are flavonoids, phenolic acids, terpenoids, volatile oils, etc. [14]. The research progress of the chemical composition of kidney tea was studied by Y. Y. Zhang's In this paper, based on a detailed review of the chemical composition of kidney tea, Y. Y. Zhang's group [14] in 2021 In this paper, the pharmacological effects and molecular mechanisms of kidney tea in the treatment of kidney-related diseases were The present paper summarizes the pharmacological effects and molecular mechanisms of renal tea in the treatment of kidney-related diseases, with a view to laying the foundation for its widespread In this paper, we summarize the pharmacological effects and molecular mechanisms of renal tea in the treatment of kidney-related diseases, with the aim of laying the foundation for its widespread use and in-depth research in the treatment of renal diseases.

 

1.1 Kidney stone model

Kidney stones are clinically manifested by the formation of a certain size in the renal pelvis or calyces The kidney stone model There are two common modeling methods: one is to give experimental animals (mice, rabbits) The first is to give the experimental animals (mice, rabbits) ip or feed them with glyoxalate, or glycolic acid, or glycolic acid plus ammonium chloride [26]. or glycolic acid, or glycolic acid plus ammonium chloride [26-27], which has the advantages of short moulding time and simple operation. The success rate of moulding was positively correlated with the amount of glyoxalate in the feed and the moulding time [15]. This method has the advantages of short moulding time and simple operation, and the success rate of moulding is positively correlated with the content of ethylenediamine in the feed and the moulding time [15]. The second is to use ethylene glycol mixed with ammonium chloride to make "stone water" for mold making. The principle is that ethylene glycol is metabolized into oxalic acid in animals, and ammonium chloride can acidify the urine, which can lead to renal tubular dysfunction after long-term administration. It can lead to renal tubular dysfunction, which is conducive to the formation of calcium oxalate crystals. This method is the most effective and stable method for stone formation [16].

1.2 Gouty nephropathy model

 

Gouty nephropathy is a kidney disease caused by the accumulation of uric acid in the body, resulting in hyperuricemia. Gouty nephropathy is a renal damage caused by the accumulation of uric acid in the body, which is mainly caused by the administration of ip or ig drugs to experimental animals (rats, mice). Gout nephropathy is caused by the accumulation of uric acid in the body, resulting in hyperuricemia. The main modalities were the administration of potassium oxyzincate, adenine or hypoxanthine, and enzyme combined with adenine. The animals were modeled by administering potassium oxyzincate, adenine or hypoxanthine and enzyme combined with adenine [17]. adenine [17], which is easy to perform and can raise the blood uric acid in a relatively short period of time.
However, the model is time-limited and can only be maintained for 5 h [28]; the modeling by ip xanthine method is short and simple, and the serum uric acid value of the model mice peaks after 0.5 h of ip xanthine and drops to half after 6 h. The uric acid abnormality in vivo can last for 24 h. However, this method often shows a one-time increase in uric acid and cannot achieve long-term and stable requirements [18]; the modeling by ig administration of potassium oxyzincate and adenine [17] is simple and reproducible. 18]; modeling by ig administration of yeast combined with adenine method [17] can better simulate the occurrence and development of human gouty nephropathy, which is in good agreement with clinical manifestations and meets the basic pathological requirements of gouty nephropathy, that is, urate crystals can trigger inflammatory pathological changes in renal tubules [29].

 

1.3 Diabetic nephropathy model

Diabetic nephropathy models can be modeled by injecting rats with STZ [19] or by feeding rats a high-fat diet or unilateral kidney removal in combination with STZ injection. The STZ injection method is easy to operate; the unilateral kidney removal combined with the STZ injection method requires a certain degree of surgical skill, and there is a possibility of postoperative infection leading to modeling failure; the STZ injection method with high-fat chow is currently the most economical and practical modeling method, and the high-fat diet can cause obesity, hyperglycemia, hyperlipidemia and other characteristics of the metabolic syndrome in diabetic patients in model animals. The model animals were injected with a small dose of STZ, which can be used for rapid and stable modeling [19].

1.4 Renal failure model

Renal failure models can be divided into acute renal failure models and chronic renal failure models. The acute renal failure (ARF) model can be used in rats or mice. The acute renal failure (ARF) model can be modeled by injecting glycerol, gentamicin, and mercuric chloride into rats or mice [1]. The model can be modeled by injecting glycerol, gentamicin, and mercuric chloride into rats or mice [20]. Gentamicin injection in rats is the most accepted method for modeling nephrotoxic ARF. Gentamicin is now the accepted model for nephrotoxic ARF, with 7 d of continuous
Gentamicin (160 mg/kg) was administered to rats for 7 d. Chronic renal chronic renal failure (CRF) can be modeled by administering adenosine or 5 mg/kg to rats. ig administration of adenine or 5/6 nephrectomy [21-23]. ig adenine The adenine modeling method is simple, has a short modeling time, and can be prepared with different doses and feeding times. The CRF models can be prepared in mild, moderate, and severe forms depending on the dose and feeding time. This modeling method is suitable for the observation and evaluation of the efficacy of drugs to restore tubular function [22]. This modelling approach is suitable for the observation and evaluation of the efficacy of drugs to restore tubular function [22]. In the case of 5/6 nephrectomy, the experimental animals can exhibit a pathological process consistent with human renal fibrosis. This method ensures that the residual kidney tissue undergoes relatively normal overload, excluding other pathogenic factors of primary renal disease This method can ensure that the residual kidney tissue is overloaded under relatively normal conditions, and excludes the influence of other pathogenic factors of primary kidney disease on the residual kidney units, simplifying the influencing factors. modeling method requires a high level of experimental technique and needs to prevent However, this modeling method requires a high level of experimental technique, the prevention of bleeding and postoperative infection, and a long modeling period.

 

1.5 Nephrotic syndrome model

The most commonly used model for nephrotic syndrome is the injection of adriamycin into rats [24]. rats with adriamycin injection [24], or unilateral The most common model for nephrotic syndrome is the injection of adriamycin into rats [24]. Unilateral adriamycin injection alone is easy to perform, but the modeling time is long. Unilateral nephrectomy combined with adriamycin injection unilateral nephrectomy combined with adriamycin injection can greatly shorten the modeling time, but it requires a certain level of surgical skill for the experimenter. The combination of unilateral nephrectomy and adriamycin injection can greatly shorten the moulding time, but requires a certain degree of surgical skill. Adriamycin is an antitumor drug containing quinone structure, which can affect the glomerular and Adriamycin is an antitumor agent with a quinone structure, which has direct toxic effects on the glomerulus and tubular epithelium and It damages the renal proximal tubule, impairs the cell membrane barrier and absorption function of the epithelial cells, disintegrates the nucleus, and causes the kidney to become a "nucleus". Therefore, the present model is not suitable for the treatment of renal tubular dilation and reduction of tubular pressure. Therefore, this model is useful for the evaluation of the efficacy of drugs with the function of dilating the tubules, lowering the tubular pressure, improving proteinuria, etc. Therefore, this model is of good value for the evaluation of the efficacy and drug screening of drugs that have the functions of dilating renal tubules, lowering tubular pressure and improving proteinuria [25].